FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 1 -
 

           References

In general 70% of sSMC carriers are clinically normal. The figures here
are based on the bias, that mainly clinically aberrant cases are reported in literature!

UPD (uniparental disomy) cases:           UPD 1   maternal   paternal   unclear  


PATIENTINFORMATION for sSMC(1)  

the probably non-dosage sensitive pericentric region of chromosome 1

 


SCHEMATIC CYTOGENETIC DEPICTION                    
sSMC-1 DISCLAIMER

 


 

SCHEMATIC MOLECULARGENETIC DEPICTION  


 

acc. to UCSC Genome Browser on Human Mar. 2006 assembly [UCSC hg18, 2006]
and available BAC-data/ array-data from cases marked *** mentioned below [MB]

 critical region 115.3--- 115.8 uncritical region   [121.10 centromere 142.40]   uncritical region ? --- ? critical region

Below adapted for UCSC hg19, 2009
 

 critical region 115.4 --- 115.9 uncritical region   [121.50 centromere 142.60]   uncritical region ? --- ? critical region

 DISCLAIMER

 


 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

1p - proximal 1q - proximal
symptoms
ataxia 5 % 0 %
autism 15 % 0 %
brain malformations 5 % 10 %
developmental delay 55 %
40 %
dysmorphic face 80 % 90 %
finger or toe/foot malformations 50 %
20 %
genital abnormalities 0 % 20 %
growth retardation 20 % 50 %
heart defect 20 % 50 %
hypotonia 15 % 0 %
joint problems 5 % 10 %
kidney problems/ malformations 5 % 10 %
mental retardation 40 %
40 %
microcephaly 40 %
10 %
overgrowth 10 % 10 %
seizures 0 % 0 %
vision impaired 5 % 0 %
number of cases (marked with “°” below) 20
10

References

Cases without clinical findings (O)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  ***
01-O-p13.2/
1-1
***
female/
32y
PBL n.a. 47,XX,+mar[78%]/
46,XX[22%]
min(1)(::p11.2q11::)
RP11-130B18 (115.8MB)
cenM, subcenM normal women, previous pregnancy child with Arthrogryposis multiplex {0} provided by Dr. Zerres, Aaachen, Germany  
  01-O-p12/
1-1
female/ 33y PBL de novo and passed to one child maternal 47,XX,+min[30%]/
46,XX[70%]
min(1)(:p11.2~12q12:)  cep probes
subcenM
Healthy woman; sSMC detected due to advanced maternal age in second pregnancy and first pregnancy with trisomy 18 {41} case 1-22  
  01-O-p12/
1-2
male/ prenatal PBL n.a. 47,XY,+min[24]/
46,XY[6]
mar(1)(:p12q1?2:) 
array-CGH: 118.326.077-120.311.644 
array-CGH,
wcp 1
Advanced maternal age; healthy young man at age of 14y {0} provided by Dr. J Lemke, Abt. Human-genetik; Uni-klinik; Inselspital; Bern, Switzerland  
  01-O-p11.2/
1-1
n.a./ prenatal PBL maternal (in 55% of PBL) 47,+r[100%] r(1)(::p11.2q10::)
RP11-115N23 (120.9MB) on 1p present on sSMC
M-FISH; cep 1/5/19; BACs{42} subcenM like;
UPD-test
Advanced maternal age; normal child {42} case 5  
  01-O-p10/
1-1
female/
prenatal newborn
AF
PBL
de novo 47,XX,+r[26%]/
46,XX[74%]
r present in only 8% of PBL 
r(1)(::p10q12::)* all available centromeric probes Amniocentesis due to low serum AFP; no ultrasound abnormalities; child normal at 9m of age {12} case 1  
  01-O-p10/
1-2
female/
prenatal newborn
chord blood; PBL de novo 47,XX,+r[40%]/
46,XX[60%] (chord blood);
in PBL sSMC in 20%
r(1)(::p10q12::)
RP11-79E5 (141.9 MB) on 1q present on sSMC 
M-FISH; cep 1/5/19; BACs{42} subcenM like;
UPD-test
Advanced maternal age; normal at birth and at 1 y {42} case 2  
  01-O-p11.1/
1-1
male/
prenatal
AF de novo 47,XY,+mar[50%]/
46,XY[50%]
min(1)(:p11.1q11:) cenM
subcenM
see below {70} case 01-O-p11.1/1-1  
Advanced maternal age; no ultrasound abnormalities; child born without abnormalities with 3500g, length 52cm, OFC 35cm, APGAR 9/10/10
  01-O-p11.1/
1-2
male/
adult
PBL de novo 47,XY,+r[70%]/
46,XY[30%]
r(1)(::p11q11::) M-FISH; cep 1/5/19; BACs{42} subcenM like;
UPD-test
Healthy male; 2 spontaneous abortions in partnership {42} case 3
{62} case 1
 
  01-O-p11.1/
1-3
female/
adult
PBL de novo 47,XX,+r[40%]/
46,XX[60%]
r(1)(::p11q11::) M-FISH; cep 1/5/19; BACs{42} subcenM like;
UPD-test
Healthy female; 5 year history of infertility {42} case 4
{62} case 2
 
  01-O-p11.1/
2-1
female/
prenatal
AF de novo 47,XX,+r[7]/
46,XX[28]
r(1)(::p11.1q21.1::) cenM
subcenM
Advanced maternal age; no ultrasound abnormalities; child born without abnormalities {39}
{41} case 1-21
 
  01-O-p11.1/
3-1
female/
31y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[100%] min(1)(:p11.1q12:) cenM
subcenM;
UPD-test
Healthy female; Familial history of repeated abortions {62} case 3  
  01-O-p11.1/
3-2
male/
44y
PBL n.a. 47,XY,+mar[53%]/
46,XY[47%]
min(1)(:p11.1q12:)* M-FISH; CGH, wcp 1; UPD-test Healthy male; habitual abortions in his wife (10x) {67} case 1  
  01-O-p11.1/
3-3
female/
prenatal
AF de novo 47,XX,+mar[5]/
46,XX[23]
min(1)(:p11.1q12:)
aCGH: no centromere-near euchromatin
cenM
subcenM
midi;
aCGH; UPD-test
advanced maternal age, repeated abortions,  healthy child born, normal at 1 y {70} case 01-
O-p11.1/3-3
{0}
 
  01-O-p11.1/
3-4
male/
44y
PBL n.a. 47,XY,+mar[64%]/
46,XY[36%]
min(1)(:p11.1q12:)* wcp 1, cep1 Healthy male; with oligoasthenozoospermia {64} case 1  
  01-O-p11.1/
3-5
female/
prenatal
AF n.a. 47,XX,+mar[18]/
46,XX[37]
min(1)(:p11.1q12:) cenM, subcenM advanced maternal age, no US abnormalities. child born and normal at 9 months. {0} provided by Dr. Mehnert, Neu-Ulm, Germany  
  01-O-p11.1/
3-6
female/
35y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[12]/
46,XX[8]
min(1)(:p11.1q12:) cenM, subcenM healthy female, detected due to abortions at age over 35y {0} provided by Dr. Mau-Holzmann, Tübingen, Germany  
  01-O-p11.1/
3-7
female/
34y
PBL n.a. 47,XX,+mar[20]/
46,XX[80]
min(1)(:p11.1q12:) cenM, subcenM healthy female, detected due to fertility problems {0} provided by Dr. Wegner, Berlin, Germany  
  01-O-p10/
1-1
male/
prenatal; newborn
CH; AF; PBL de novo only in chorionic cells: 47,XY,+mar[2]/
46,XY[28]
no sSMC in 100 PBL cells postnatally
min(1)(:p10q12:) cenM
subcenM;  UPD-test
advanced maternal age and mucoploysaccaridose II with known mutation (c708G>A) in mother; no mar in amnion cells; healthy child born {0; 70} case 01-O-p10/1-1  
                     

 

 O-Cases with similar imbalances NOT caused by sSMC (O-IMB):

 

 

                   
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  01-O
IMB
q11/
1-1
male/
9y
PBL maternal 46,XY,dup(1)(q11q22) CGH, YAC in 1q22 (930F5 - not in UCSC) detected in child with T-lymphoblastic leukemia; mother an three other family members normal {53}  
                   

 

O-cases with unclear/insufficient characterization of the sSMC (CO):

 

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  01-
CO-1 
male/
prenatal
AF maternal 47,XY,+mar[100%] ish mar(1)(D1Z5+) different FISH-probes:
D1Z5; 
Healthy male; mother healthy as well {9} case 15  
  01-
CO-2
female/
prenatal
AF
cell line at ECACC DD0943
de novo 47,XX,+mar[100%] mar(1) .ish(cep1+;wcp1-) all centromeric probes; wcp 1; UPD-test born clinically normal {4} case 1
{19} case 1
 
  01-
CO-3
male/
25y
PBL n.a. 47,XY,+mar[10%]/
46,XY[90%]
r(1) all centromeric probes born clinically normal; marker detected due to CML disease {15;16} case 17  
  01-
CO-4
male/
1y
PBL de novo 47,XY,+mar[?%]/
46,XY[?%]
dic(1) all centromeric probes normal at 1 y {38} case 7  
  01-
CO-5
n.a./
prenatal
AF maternal 47,+mar[?%] r(1) n.a. normal mother, sSMC found prenatally in 2 subsequent pregnancies {69} 1 case  
                     

 


References

Cases with clinical findings (W)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  01-W-
p2?/
1-1
n.a./
postnatal
PBL de novo 47,+mar[25%]/
46[75%]
r(1)(::p2?q1?::)*
size >13.9 MB
n.a. and subcenM with 3 BACs mental retardation (mild)
 
{51} case 2  
  01-W-
p21.3/
1-1
female/
n.a.
PBL n.a. 47,XX,+mar[100%] r(1)(::p21.31q25.2::)
98.25-174.81 MB
midi; array CGH Stickler-syndrome like, i.e. dysmorphic face, vision impaired hearing loss, joint  problem {0} provided to Dr. G. Senger, by Dr. Brondum-Nielsen, Denmark}  
  01-W-
p21.1/
1-1
moved to 01-U-10 {22, 80}  
  01-W-
p21.1/
2-1  °
male/
prenatal
AF de novo 47,XY,+mar[10/
46,XY[11]

min(1)(:p21.1p11:)
104.9-129.5 MB [hg19]

aCGH; FISH advanced maternal age; TOP; autopsy: hypotelorism, low-set ears, micrognathia, bulbous nose, small mouth clinodactyly {81}  
  01-W-
p13/
1-1  °
female/
5y
PBL de novo 47,XX,+r[30%]/
46,XX[70%]
r(1)(::p13q10::)*  see below mild DD, minor dysmorphism {8} case B  

FISH: D1Z1; BAC923C6 in 1p12 and RR6 in 1q12; midi-probe of case D in Ref {8}

  01-W-
p13/
1-2  °
female/
1y
PBL de novo 47,XX,+r[30%]/
46,XX[70%]
r(1)(::p13q10::)  midi; UPD test see below {5} case A  

Born at term after uneventful pregnancy; birth w: 3,800g; at 6y: DD (sitting not before 1y); at 13 y no walking without support); severely MR with autistic symptoms, no speech; general muscular hypotonia in combination with ataxia; growth retardation weight -2 SD, but normal height (+1 SD); dysmorphic face (cleft palate, long face with small, up-slanting palpebral fissures, long nose, small chin, featureless philtrum, micrognathia, high arched palate).

  01-W-
p13/
2-1  °
male/
15m
PBL de novo 47,XY,+r[20]/
46,XY[80]
r(1)(::p1?3q1?1::)*  different FISH-probes:
D1Z5, wcp
see below {11}   

Delivery by cesarean section <--  breech position of fetus; born at 36 weeks; birth w: 2,600g; l: 47.5cm; at 1y DD (sitting; standing with support); delay of ~6m in development; dysmorphic face (asymmetric skull with plagiocephaly, flat occiput; double vertex hair whorl, epicantal folds, slight hypertelorism, protuberant eyes); clinodactyly of 4th toes; general hypotonia; anxious and over excitable behavior

  01-W-
p13/
3-1
female/
1w
AF de novo 47,XX,+r[6]/
46,XX[19]
r(1)(::p13q21.3::) midi see below {13} case 3  

Prenatal: polyhydramnion and two-vessel umbilical cord; born in week 35, growth retardation, microcephalus (<3rd percentile), normal length; dysmorphic face (mild brachycephaly, small anterior fontanel, micrognathia, cleft palate, abnormal ears); hypoplastic nails; patient died 6 weeks later.

  01-W-
p13/
4-1
male/
15y
PBL de novo 47,XY,+r[13]/
46,XY[80]
r(1)(::p13q23::) wcp probes 1, 9, 16 see below {10}  

pregnancy complicated by mat. hypertension; birth w: 2,727g; l: 48cm; APGAR  5/10; at birth: bilateral glaucoma; at 4 m: failure to thrive; at age of 23 m no sitting or walking, growth retardation: weight and length <3rd centile; at 3.5y: cataract formation in right eye; at age of 8.5y seizures started; at age of 15y: confined to wheelchair; severe psychomotor retardation; small and short stature; microcephaly; megalocornea; dysmorphic face (up slanted palpebral fissures, short philtrum, cupped ears).

  01-W-
p13.3/
1-1 °
male/
4.25y
PBL/ buccal mucosa de novo 47,XY,+r[7]/
46,XY[43]
(in buccal mucosa 3 signals in 9%)
r(1)(::p13.3q10::)  midi; wcp1, cep1, YAC for 1p13.2 see below {18}   

Prenatal: normal in week 20; birth by cesarean section  <- breech position + umbilical cord compression in week 42; birth w: 3,025g (10th centile); l: 51cm (50th centile); OFC: 34cm (10-25th centile); APGAR 9/10/-; motor development and global development delayed (walking 3y; no speech up to 3.5y); at 4.25y w 14kg (3rd centile), h 106cm (50th centile); microcephaly; dysmorphic face (myopatic face with open mouth at rest, mild ptosis, mild hypertelorism, slight down-slating palpebral fissures, epicanthic folds, over folded helices with mild ear protrusion); short 5th finger with clinodactyly, congenital hypotonia, hyper extensibility of joints, severely MR, attention deficit disorder, auto aggressive episodes, autistic symptoms.

  01-W-
p13.3/
2-1
male/
~2y
PBL de novo 47,XY,+mar[3]/
46,XY[14]
r(1)(::p13.3q21.2::)
112.16-148.40 MB
CHG, subcenM, midi, array-CGH see below {0} provided by Joana Melo  (Coimbra, Portugal)  

10y: DD and learning difficulties 11y: no DD any more,  adequate growth (h: 148.5 cm; w: 44kg; OFC 51.25 cm; 10-25th centile), urethral problems: bilateral vesiculo-uretral reflux, bilateral inguinal hernia + dentition problems. (corrected)

  01-W-
p13.3/
3-1   °
male/
prenatal
AF n.a. 47,XY,+mar[13]/
46,XY[8]
mar(1)(:p13.3?q11.1:)* aCHG, M-FISH see below {74} case 1  

amniocentesis due to advanced maternal age; due to sSMC termination of pregnancy at 26 weeks; autopsy: deep set infra-orbital creases, blepharophimosis, hypertelorism, broad nose, long philtrum, big mouth, bilat. camptodactyly, liver hypoplasia

  01-W-
p13.3/
4-1   °
n.a./
prenatal
fibro
(from fetus
after TOP)
de novo 47,+mar[57%]/
46[43%]
r(1)(::p13.3q1?::)* 
size 13.7 MB
n.a. and subcenM with 3 BACs see below {51} case 1  

IUGR of ~2 weeks, heart defect (single umbilical artery, small echogenic intracardiac focus), no over fetal anomalies noted in ultrasound at 18 2/7 weeks, TOP

 


01-W-

p13.2/
1-1 °

male/
prenatal
 AF/
PBL
de novo in AF: 48[13]/47[7]
PBL: 48,XY,+mar1, mar 2[20]/
47,XY,+mar1 or 47,XY,+mar2[7]/
46,XY[3]
mar1: der(1)(:p13.2q11:)
distal clone in p RP11-315M1 (114.0MB)
mar2: der(1)(:p11
q12:)
distal clone in q RP11-20J19 (141.3MB)
different cep probes. different BAC probes see below {20}   

Advanced maternal age and cleft palate prenatal. At term birth; w: 3,230g, unilateral cleft lip and palate, hypoplastic aortic arch, ventricular septal defect, patent ductus arteriousus.

  ***
01-W-
p13.2/
1-2   °
 
***
male/
prenatal
 AF n.a. 47,XY,+mar[13]/
46,XY[8]
mar(1)(:p13.2q1?:)
aCGH: 115.3-121.4 MB
aCGH see below {79}  case 3
 

Advanced maternal age; TOP - autopsy: facial dysmorphism, bilateral camptodactyly and spleen hypoplasia

 
01-W-

p13.2/
2-1
female/
10y
PBL de novo 47,XX,+mar[18]/
46,XX[32]
r(1)(:p13.2q23.3:)
112.75-158.6 MB
SKY,
aCGH
see below {76}   

Nomal pregnancy, at 6y: developmental delay, speech delay, unstable gaits, kyphoscoliosis, hyporeflexia, facial asymmetry, round face, depressed nasal bridge, epicantus, dysplastic, lowset ears, hypertelorism, prominent forehead, 5x5cm subcutaneous mass over occipital scalp = dermatofibrosarcome protuberans. weight 50 centile, heigth 85 centile; at 8y seizures, at 10y multiple exostoses over left thigh and osteochondroma

  01-W-
p12/
1-1
female/
3.5y
PBL de novo 47,XX,+r[5]/
46,XX[45]
min(1)(:p12q11:)  cenM
subcenM
see below {39}
{41} case 1-7
 

Born at term after uneventful pregnancy (at 41 weeks); birth w: 3,035g; l: 47,5cm; OFC: 34cm; hypertonic crisis with cyanosis 48 h after birth, and afterwards alternate hypotonia episodes with irritability crisis. With 3 m w of 4,250 g (5-10th centile),  l 38cm (10-25th centile), dysmorphic face (mild facial angioma, low set ears, thin upper lip with a prominent philtrum, blepharophimosis); thin skin with eczemas; DD, psychomotor delay

  01-W-
p12/
2-1 °
female/
1.5y
PBL de novo 47,XX,+mar[15] min(1)(:p12q12:) 
(no telomere signals)
aCGH - 1p13.2p11 (112,435,112-121,023,900 Mb)
 
cenM
subcenM
telomere-FISH
aCGH
 
psychomotor retardation; dysplasia of the kidney; seizures; retinal bleeding; chronically bronchitis. {1} case 11
{2} case 5
{0}
{78} case Sm-1
 
  01-W-
p12/
2-2
female/
28y
PBL de novo (? father n.a. for study) 47,XX,+mar[50%]/
46,XX[50%]
min(1)(:p12q12:)  wcp1
subcenM-FISH
see below

 

{41} case 1-9  

During pregnancy kidney problems of the mother; born 6 week preterm; birth w 2,250g; torticollis spasmodicum corrected at 10m; MR, focal epilepsy due to Arnold-Chiari-syndrome since 18m; w at 19y: 93kg = >P97; h: 172cm; OFC: 55.5cm; facial dysmorphism (asymmetry of the skull, hypertelorism, dysmorphic ears); sec. amenorrhea due to climacteric praecox caused by hormonal insufficiency

  01-W-
p12/
2-3 °
female/
1m
PBL de novo 47,XX,+mar[15%]/
46,XX[85%]
r(1)(::p12q12::)*  midi; different FISH-probes:
D1Z1; probe BAC923C6 in 1p12 and RR6 in 1q12
see below {8} case D  

Large protruding tongue, small ventricular septal defect at birth, at age of 2y normal development

  01-W-
p12/
2-4 °
female/
44y
PBL de novo (?) 47,XX,+mar[8]/
46,XX[13] (at 35y); 
at 42y mar in only 3/20 cells
r(1)(::p12q12::) cenM
subcenM
see below {41}case 1-10  

Birth w 2,300g, subsequent feeding problems; severe DD: no speech; generalized epilepsy (since childhood); since age of 12y psoriasis vulgaris; short stature (150 cm) microcephaly (HC 48 cm); dysmorphic face (asymmetric, low frontal hairline, ptosis, epicanthic folds prominent lips); mild camptodactyly of the fingers, short toes; has a full range of movements but has difficulty in mobility. CT scan: cortico-subcortical atrophy with wide ventricles and sulci.

  01-W-
p12/
2-5 °
male/
3y
PBL de novo 47,XY,+mar[7%]/
46,XY[93]
r(1)(::p12q12::) SKY, BAC 923C3 in 1p12 see below {50}case 7  

Born in week 38 of gestation. Birth w: 2,650g; at 1y mild DD and physical abnormalities; at 2y started walking but not speaking. Dysmorphic face (microcephaly, hypertelorism, almond like palpebral fissure, protruding eyes, anteverted nostrils); brachyclinodactyly of 5th fingers, tapering fingers.

  01-W-
p12/
2-6  °
n.a./
n.a.
PBL n.a. 47,+mar[100%] mar(1)(::p12q12::)* 
120.49-141.48MB
array-CGH DD MR; epicantal folds, low set ears, autistic features {0} provided by Dr. SW Cheung, Houston, USA  
  01-W-
p12/
2-7   °
female/
prenatal  
CH   n.a.   47,XX,+mar[4]/
46,XX[12]
mar(1)(::p12q1?::)* 
120.21-121.30 MB
array-CGH Increased NT> 4,55mm; TOP: Facial
dysmorphism,
ventricular
septal defect
and foot
abnormalities
{79} case 2    
  01-W-
p12/
3-1  °
male/
1m
PBL de novo 47,XY,+mar[80%]/
46,XY[20%]
r(1)(::p12~11q12::)*  wcp 1, centromere-near YACs as specified in {17} see below {17} case 2  

At birth w: 3,939g, l: 52.5cm, APGAR 7/10; right talipes equinovarus; at 2y hyperactivity, and attention deficit disorder.

  01-W-
p12/
3-2 °
male/
10y
PBL de novo 47,XY,+r[15%]/
46,XY[85%]
r(1)(::p12~p11q12::)* wcp1, D1Z7 see below {21}  

Born at term after uneventful pregnancy apart from polyhydramnion; excessive drooling ups up to 4y of age; atopic dermatitis, DD in all motor skills, at 10y poor concentration ability and inattentive, dysmorphic face (telecanthus, flat nasal bridge, up slanting palpebral fissures, prominent and swollen eyelids, midface recessed, long philtrum, low-set ears, high arched palate, short neck and low posterior hairline, HC at 98. centile); language delay; mental handicap

  01-W-
p12/
4-1  °
male/
prenatal
AF de novo 47,XY,+mar[13]/
46,XY[8]
mar detected in skin, lung, heart, kidney as well
inv dup(1)(:q12p12::p12q12:)*  midi; 
subcenM;
M-FISH
see below {33}   

Advanced maternal age; normal ultrasound, TOP in 25th week; Autopsy: slight craniofacial dysmorphism, bilateral camptodactyly, rocker bottom feet, but no organ malformation.

  01-W-
p12/
5-1
female and male/
postnatal
PBL maternal
(16% only - mother mildly affected)
47,+mar[71% or 54%]/
46[29% or 46%]
r(1)(::p12q21.1::) 
118.27-146.58MB
wcp, cep, array-CGH facial dysmorphism, low weight, camptodactyly of fingers 4 and 5, DD {73}   
  01-W-
p12/
5-2
female/
postnatal
PBL de novo 47,XX,+mar[41]/
46,XX[150]
r(1)(::p12q21.1::) 
~0.8MB in 1p and ~1.91 MB in 1q in euchroimatin
pericentric BAC set facial dysmorphism, drug resistant focal seizures, MR
{82} case 2  
  01-W-
p11.2/
1-1
female/
3.5y
PBL de novo 47,XX,+mar[10%]/
46,XX[90%]
r(1)(:p11.2q24:)*
size 14.2-17.8 MB
n.a.; subcenM with 3 BACs see below {51} case 3  

DD; no walking or speaking at 33 months of age, although she does point, smile, and use some signs to communicate; dysmorphic features; strabismus; hyperopia; hydronephrosis; normal growth parameters at 15 and 33 months of age.

  01-W-
p11.2/
2-1
male ?/
7y
PBL de novo 47,+mar[66%]/
46[34%]
mar(1)(:p11.2q1?:) n.a.; array CGH see below {51} case 4  

Behavior problems; autistic features; speech delay; mild MR; IQ = 68; at 7 ½ years of age the patient functions at a 5-year-old level.

  01-W-
p11.2/
2-2   °
male/
prenatal
CH de novo 47,XY,+mar[10]/
46,XY[16]
mar(1)(:p11.2q1?:)* cep; array CGH see below {74} case 2  

CVS due to cystic hygroma, TOP in week 26; pathology: dolichocephaly, high forehead, nose with large nares, deep set infra-orbital creases, ears not hemmed, 5th toe camptodactyly, long toes and fingers, excess skin. nuchal edema

  01-W-
p11.2/
3-1  °
male/
14m
PBL de novo 47,XY,+r[15%]/
46,XY[85%]
r(1)(::p11.2q12::)
BAC-breakpoint mapping:
120.84MB and 141.6 MB
M-FISH; cep 1/5/19; BAC probes as specified {42} subcenM like; UPD test see below {42} case 1  

Caesarian section at 32 weeks after IUGR; APGAR 8/9; at birth: w 910g (<3rd centile), l 34 cm (<3rd centile), OFC 27 cm (5th centile); at birth severe respiratory distress. At 14m all values persisted <3rd or ~5th centile. Psychomotor retardation, facial dysmorphism (face triangular with high forehead, frontal bossing, sparse eyebrows, long eyelashes, ectropion, anteverted nostrils, long philtrum, thin upper lip, high-arched palate, and small pointed chin, ears low-set with flat antihelices), body asymmetry and hypoplastic right side; pectus excavatum; cryptorchidism.

  01-W-
p11.1/
1-1
female/
8y
PBL de novo 47,XX,+mar[8]/
46,XX[12]
min(1)(:p11.1q12:) cenM
subcenM
see below {41} case 1-14  

Born at 7th month; w: 2,350g, l 46cm; twin brother compared to which patient is retarded; no malformations apart from dysmorphic face and mild psychomotor retardation

  01-W-
p11.1/
1-2
female/
2y
PBL de novo 47,XX,+mar[60%]/
46,XX[40%]
min(1)(:p11.1q12:) cenM
subcenM
see below {0} provided by Dr. Anikó  Ujfalusi, Hungary  

Born in 38. week after normal pregnancy; w: 3,050g; at 8 months: psychomotor DD; at 12 month: sitting, at 14 month: corpus callosum agenesis (MRI); at 27 months standing, MR; dysmorphic face (prominent forehead, irregular hair line, epicanthus on both side, markedly broad nasal root); clinodactyly of fifth finger, syndactyly between toes II and III, lateral deviation of feet and toes. Family history: Mother with cleft lip at birth. Father: severe CMV infection at the time of conception, the antibody titer of the mother during the pregnancy was normal/borderline

  01-W-
p11.1/
2-1  °
male/
1m
PBL de novo 47,XY,+r[48]/
46,XY[52]
r(1)(::p11.1q21.1::) cenM
subcenM
see below {41} case 1-15  

Born at 36 week by cesarean section; podalic presentation; w: 2,240g (3-25th centile), l: 43.5 cm (10-25th centile), OFC: 31 cm (10-25th centile). dysmorphic face (repaired cleft lip, big and low-set ears, microretrognatia); angioma in the back.

  01-W-
p11.1/
2-2 °
male/
1y
PBL de novo 47,XY,+r[5]/
46,XY[45]
r(1)(::p11.1q21.1::) cenM
subcenM
MCB
see below {2} case 4
{3} case 4
 

Clinical signs similar to DiGeorge syndrome, however, no microdeletion 22q11.2 ; DiGeorge syndrome includes: heart defect, immune deficiency, dysmorphic face

  01-W-
p11.1/
2-3  °
male/
1w?
PBL de novo 47,XY,+r[50%]/
46,XY[50%]
r(1)(::p11.1q21.1::)* wcp 1, centromere-near YACs as specified in {17} see below {17} case 1  

born with w: 2,960g, l: 49.5cm HC: 32cm; resuscitation needed postnatal due to severe respiratory distress; dysmorphic face (long philtrum, low hairline; high arched palate); limbgridle muscular hypotrophy; hypospadias with undescended testicles; bilateral club-foot; intestinal occlusion due to volvulus; infant died at 22 m.

  01-W-
p11.1/
2-4  °
female/
2m
PBL de novo 47,XX,+mar[30%]/
46,XX[70%]
min(1)(:p11.1q11:)[50%]/min(1)(:p11.1q21.1:)[50%] cenM, subcenM see below {0} provided by MUDr. Jana Lastuvková, Ústi nad Labem, Czech Republic  

IUGR; birth at 29th week due to anhydramnion; congenital malformations: hypertrophic cardiomypathy, small mandible, dysmorphic face (dysplastic low set ears), limited joint movement; child died at 2 months of age

  01-W-
p11.1/
3-1 °
male/
prenatal
AF and
various tissues
(EKF-
cellbank)
de novo 47,XY,+r[8]/
46,XY[52]
sSMC present in 13 to 60% of studied fetal tissues
r(1)(::p11.1q22::)
array-CGH: 105.98-188.41MB
r(1)(::p21.1q31.1::)
centromeric-probes, subcenM, MCB
array-CGH
see below
{0}{43} case 1
{47}
 

Heart defect detected in ultrasound - coarctation of aorta in week 20; holes in wall between chambers in week 24; TOP, postmortem report: no external or intracranial anomalies, apparently normal cardiac connections with probable tubular hypoplasia of aortic arch and coarctation at ductal level (weight: 1,975g, OFC: 31.5 cm); horseshoe kidney.

  01-W-
p11/
1-1 °
female/
3y
PBL de novo 47,XX,+r(1)(::p11→q22::)[15]/
47,XX,+r(1)(::p11→q22::q22→p11::)[45]
46,XX[340]
n.a. n.a. see below {29}   

Pregnancy complicated with high fever of unknown origin in 3rd month; delivery at term by cesarean section because of pelvic presentation; w: 2,900g; walking at 30m; at 37m height between 80.-90. centile, OFC at 60. centile, weight 17.5kg; dysmorphic face (round face, very low hair line, frontal hypertrichosis, thin curved eyebrows, slanting palpebral fissures, short wide nasal bridge, cavernous hemangiomas on right nasal side, anteverted nostrils, long wide philtrum, fish shaped mouth); short hands an feet, bilateral clinodactyly 5

  01-W-
p11/
2-1
male/
prenatal; newborn
AF and PBL de novo 47,XY,+mar[19]/
46,XY[1]

in PBL mar in 26/30 metaphases
r(1)(:p11q11:) all centromeric probes, telomeric probes see below {35} case 6  

Advanced maternal age; born at term by cesarean section and phenotypically normal. At 2 years was noted to have mild speech delay; had a raised strawberry hemangiomas in center of chest, but otherwise phenotypically normal.

  01-W-
p11/
3-1
female/
2y
 PBL n.a. 47,XX,+mar[35]/
46,XX[15]
min(1)(:p11q11:) midi;
subcenM
clinically abnormal {78} case Sr-1  
  01-W-
p11/
4-1  °
male/
2y 
 PBL de novo 47,XY,+mar[12]/
46,XY[48]
 r(1)(::p11q23.3::)
aCGH: 143,88-162,88
 
cenM;
subcenM; aCGH
 
see below {0} provided by Dr. Kowalska-Pawlak, Poland  

at 2 y: facial dysmorphism, MR, complex congenital malformations, tetralogy Fallot, cryptorchism, psychomotor retardation

  01-W-
p10/
1-1 °
female/
13y
PBL de novo 47,XX,+r[35%]/
46,XX[65%]
r(1)(::p10q22::q22q21.3::)* YACs as described in {26} see below {26}   

Born at term after normal pregnancy; birth w: at 25. centile, l: at 10. centile, OFC: <3rd centile, APGAR 8/10/10; microcephaly, dysmorphic face (asymmetric and abnormal low set ears, broad nasal bridge, high arched palate, micrognathia); pilonidal dimple; cardiac murmur; cardiomegalie; chest asymmetry, VSD; psychomotor delay; growth retardation; kyphoscoliosis; at 15y microcephaly, dysmorphic face (low frontal hairline, down-slanting palpebral fissures, broad nasal bridge, large nose, short neck), hirsutism; MR; no speech.

  01-W-
p10/
1-2 °
female/
3.5y
PBL de novo 47,XX,+r[8]/
46,XX[92]
r(1)(::p10q21::p10q21: :p10q21::)* YACs and BACs as described in {30}; midi; CGH; UPD test see below {30}   

Born at term after normal  pregnancy; Birth w, l and OFC on the 3rd centile. At 1y statomotoric retardation; muscular hypotonia; microcephaly; dysmorphic features (mild high-arched palate, epicanthal folds); sitting at 1y. Up 2y no walking or standing upright without support; lack of language development, audiological tests normal. At 3.5y language and motor development delay; able to walk but used no language. Head circumference, height and weight between the 3rd and 10th centile. Motor skills and social interaction were decreased without autistic symptoms plus an attention deficit disorder. At seven years, progressed due to a special kindergarten program and showed age-matched social interaction.

  01-W-
p10/
2-1 °
female/
4.3y
PBL de novo 47,XX,+mar[>95%/ 47,XX,+?r[~2%]
46,XX[<3%]
min(1)(:p10q12::q12q21.2: :q21.1~21.2q21.1:)* YACs and BACs as described in {34}; midi see below {34}   

Born at term after normal pregnancy; birth w and l 10th centile, OFC >20th centile; dysmorphic face (asymmetry, hypertelorism, low-set ears, micrognathia, broad nasal bridge, short philtrum, dimple between lower lip and chin, high palate, prominent occiput); simian crease; sacral dimple; at 9 m DD  of at least 2 months but no growth retardation; psychomotor developmental delay of ~1y; at 5.5y her language abilities had improved, she was able to form whole sentences, but she had difficulties to concentrate

                     

 

 

W-Cases with similar imbalances NOT caused by sSMC (W-IMB):

 

                   
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  01-W-
IMB-
q11/
1-1
male/
postnatal
PBL de novo 46,XY,dup(1)(q12q23) n.a. Severely retarded, psychomotor development, growth retardation, and multiple congenital malformations. {57}  
  01-W-
IMB-
q11/
2-1
female/
3y
PBL de novo 46,XX,dup(1)(q11q25) no FISH resembling Proteus syndrome, i.e. skin overgrowth and atypical bone development. {54}  
  01-W-
IMB-
q12/
1-1
female/
1m
PBL de novo 46,XX,dup(1)(q12q21) SKY; BAC-FISH see below {63}  
Suggestive of Turner syndrome; dysmorphic face (prominent nose, low-set, crumpled ears, slightly high palate); short neck,; high-pitched cry; mild micrognathia; hypoplastic labia majora, somewhat deep palmar creases.
  01-W-
IMB-
q12/
2-1
female/
16y
PBL de novo 46,XX,der(X)ins(X;1)(q21;q12q21) wcp FISH Behavior and learning problems - the inserted part is subject to random X-inactivation {65}  
  01-W-
IMB-
q12/
2-1
female/
18y
PBL de novo mos 46,XX,dup(1)(q12q22)/
46,XX
n.a. Mentally handicapped. {56}  
  01-W-
IMB-
q12/
3-1
female/
postnatal
PBL de novo 46,XX,dup(1)(q12q21.3) wcp 1 see below {59}  
Developmental delay, macrocephaly, dysmorphic face (asymmetry, small down turned palpebral fissures, high and narrow palate, micrognathia), short neck, a heart defect, and unilateral renal agenesis.
  01-W-
IMB-
q12/
4-1
female/
postnatal
PBL de novo mos 46,XX,dup(1)(q12q23)/
46,XX
n.a. multiple clinical abnormalities {55}  
  01-W-
IMB-
q12/
5-1
male/
postnatal
PBL de novo 46,XY,dup(1)(q12q25) wcp 1 see below {58}  
Excessively wrinkled skin, mild micro/brachycephaly with mild hydrocephalus and slightly small temporal lobes, apparently low-set ears, retro/micrognathia and cleft soft palate (Pierre-Robin anomaly,) patent ductus arteriousus and foramen ovale, pulmonary hypoplasia, eventration of the left hemidiaphragm, right cryptorchidism, a sacral dimple, flexion contractures of fingers and knees, and equinovarus deformities of both feet
                   

 

W-cases with unclear/insufficient characterization of the sSMC (WO):

 

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  01-
CW-1
male/
2.5y
PBL de novo 47,XY,+mar[70%]/
46,XY[30%]
r(1)(::q11p11.2::1?::) FISH with all centromeric probes:
D1Z1; BAC923C6 in 1p12, RR6 in 1q12; midi-probe of case D {8}
see below {7} case 1
{8} case C
 
Delayed speech and dysmorphic face (long face, ear-lobule creases, slightly up-slanting palpebral fissures, long nose with broad nasal bridge, mild micrognathia), bilateral clinodactyly of the 5th fingers and inverted nipples.
  01-
CW-2
male/
8y
PBL de novo 47,XY,+mar[30%]/
46,XY[70%]
r(1)(::q11p11.2::1?::) different FISH-probes:
D1Z1; BAC923C6 in 1p12, RR6 in 1q12; midi-probe of case D{8}
minor dysmorphic features, moderately intelligent at age of 12y {8} case A  
  01-
CW-3
female/
7.5y
PBL de novo 47,XX,+mar[11]/
46,XX[49]
r(1)(wcp1+,D1Z1/D5Z2/D19Z3+) wcp1; cep1/5/19 see below {0} provided by Dr. Peter Kannu (Auckland, New Zealand)  
Mild intellectual disability; height 75th centile, weight 97th centile, head circumference 2nd centile; dysmorphic face (brachycephaly, wide & depressed nasal bridge, epicanthus, bilateral ptosis, hypermetropia); hypotonic, generalized hypermobility; moderate bilateral hearing loss of high frequency.
  01-
CW-4
female/
79y
PBL de novo 47,XX,+mar[3]/
46,XX[50]
r(1)(wcp1+) wcp1 see below {32}  
Born at term (weight: 3,150g = 25th centile, OFC 31 cm = <10th centile), seizures from 4 months of age; at 2y no speech, gross motor delay, dysmorphic face (brachycephaly, asymmetric epicanthic folds, mild hypertelorism, thick bushy eyebrows, brachycephaly); at 5y walking but no speech; at 9y still speech and gross motor delay, epilepsy and behavior similar to Rett-syndrome.
  01-
CW-5
male/
5y
PBL
(EKF-
cellbank)
paternal ?
mar in 2/50 metaphases
47,XY,+mar[17]/
46,XY[3]
min(1)(:p11.1q11:)
no centromere-near euchromatin detectable
cenM; aCGH Clinically abnormal; suspicion of fra(X) syndrome, developmental delay. {0} provided by Dr. Mehnert (Neu-Ulm, Germany)  
  01-
CW-6
male/
prenatal
AF de novo 47,XY,+mar[13]/
46,XY[8]
mar(1) 'pericentric region of 1p and 1q' M-FISH, wcp 1, subtel 1p and 1q, midi see below {44}  
Advanced maternal age; TOP; autopsy in week 25 revealed slight craniofacial dysmorphism, bilateral campodactylia, rocker bottom feet, no organ malformations.
  01-
CW-7
male/
10y
PBL n.a. 47,XY,+mar[32%]/
46,XY[68%]
r(1) .ish (wcp+, D1Z1-) wcp1; cep1 Mentally retarded without dysmorphic features. {64} case 2  
  01-
CW-8
n.a./
prenatal
AF de novo 47,+mar[38%]/
46[62%]
r(1) wcp1; cep1 Sonographic malformations: IUGR, TOP. Fetopathology: Growth failure, hypotrophic placenta. {66} case 11  
                     

 


References

Cases with unclear clinical correlation (U)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  01-
U-1
female/
13y
PBL de novo 47,XX,del(18)(q22),+mar[25%]/
46,XX,del(18)(q22)[75%]
r(1)(:p?11.2q?21.1:)* radioactive ISH; satellite II  probe for chr. 1 see below {6} case 1  
Normal pregnancy and delivery; At age of 13: microcephaly, short stature, moderately severe mental retardation, myopia, dysmorphic facial features, congenital nystagmus spina bifida occulta of S1; in the past: bilateral vesicoreteric reflux, chronic serous otis media.
  01-
U-2
see mult 2-11      
  01-
U-3
n.a./
n.a.
n.a. n.a. 47,+mar[?%] mar(1) centromeric probes no info available {46} 1 case  
  01-
U-4
female/
prenatal 
AF de novo 47,XX,+mar[46]/
46,XX[8]
r(1)(:p11q11:) all centromeric probes, telomeric probes see below {35} case 8  
Amniocentesis due to a positive screen on expanded AFP for trisomy 21 with an estimated risk of 1: 42; ultrasound at 22 4/7 weeks gestation was normal. The patient was lost to follow-up.
  01-
U-5
female/
prenatal
CH de novo 48,XX,+mar,+mar[2]/
47,XX,+mar[28]/
46,XX[20] mar only in long term culture of CH; not in AF not in PBL
min(1)(:p11q12:) 3 variants in size of 1q12 cenM;
subcenM;
UPD test
see below {0} provided by Dr. A. Dufke, Tübingen, Germany  
clinically abnormal in ultrasound; plexus choroideus cysts, hypoplastic cerebellum, conspicuous finding for heart; marker only in CV, not in amniocytes and not in blood, postnatally. Ultrasound-abnormalities were detected, postnatal suspected to suffer from Aicardi-syndrome. Child deceased a few years after birth.
  01-
U-6
male/
prenatal
AF de novo 47,XY,+mar[8]/
46,XY[22]
r(1)(::p21q21::) cep probes; SKY, midi see below {48}  
prenatal diagnosis due to advanced maternal age. No ultrasound abnormalities, TOP in week 23 of gestation. In autopsy no abnormalities detected.
  01-
U-7
female/
prenatal
AF de novo 47,XX,+mar[7]/
46,XX[21]
r(1)(::p11.1q21.1::) centromeric probes; RP5-940; AL157950; RP11-35B4; AL359093);
UPD test
no clinical information available {40} case 34  
  01-
U-8
see mult 2-25      
  01-
U-9
female/
prenatal 
AF de novo 47,XX,+mar[8]/
46,XX[15]
min(1)(:p11.1q21.1:)[19]/
min(1)(:p11.1
q21.1:)x2[3]
cenM; subcenM; UPD test advanced maternal age, no US abnormalities, TOP {0} provided by Dr. Hickmann (Düsseldorf, Germany)  
  01-
U-10
female/
6y
PBL de novo 47,XX,+mar[14]/
46,XX[26]
r(1)(::p21.1q12::)
mat UPD 1
midi; telomeric probes; UPD test see below {22; 80}   
Born at term after uneventful pregnancy; birth weight: 2,500g; length: 49cm; OFC: ?; at 6y: mental retardation; height: normal; weight normal; HC 44cm (<3rd centile); dysmorphic face (additionally temporal narrowing, downward slanting palpebral fissures, long eyelashes, high palate, pointed chin, low set, dysplastic ears); hip dysplasia, tapering fingers with clinodactyly of fingers 2, 4, 5.
  01-
U-11
male/
prenatal 
AF de novo 47,XY,+mar[?%]/
46,XY[?%]
mar(1) SKY n.a. {75} case F0414116
 
  01-
U-12
female/ 7y PBL de novo 47,XX,+mar[44]/
46,XX[256]
mar(1) SNP-array normal at birth; then feeding problems, delayed motor milestones and speech development {77}  
  01-
U-13
female/
prenatal
AF n.a.

47,XX,+mar.ish add(1)(porq)[47]/
48,XX,+2mar.ish (wcp1,D1Z1)x2[13]/
46,XX[40]

complex mar(1)x2
1.66Mb duplication arr 1p33p34.1 (45,566,167-47,233,827)x3,
355kb duplication arr 1p31.1(77,819,029-78,174,408)x3
7.78Mb duplication arr 1p22.2p31.1 (81,784,564-89,570,359)x3
528kb duplication arr 1p13.3 (110,488,176-111,169,53)x3
5.96Mb duplication arr 1p12p13.2 (114,488,799-120,449,334)x3
FISH; aCGH

Microcephaly
R>1/41
increased NT>
6.5mm

{79} case 1  
  01-
U-14
female/
postnatal
PBL de novo

47,XX,+mar[?]/
46,XX[?]

min(1)(:p12?q10:)
at least 1.14 Mb in 1p12 in euchroimatin
pericentric BAC set

n.a.

{82} case 1  
                     

 

 


References

Cases with neocentromeres (N)

 

                     
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result
grade of mosaicism
final result of the sSMC test
methods
clinical symptoms reference  
  01-N-
p32/1-1
see McCl-01-N-p32/1-1   {24; 25; 31; 36; 52}  
  01-N-
p22/1-1
male/
prenatal
AF de novo 47,XY,+mar[?%]/
46,XY[?%]
r(1)(::p22p21::) CGH see below {45} case 14  
Enhanced nuchal translucency (>4mm); in 24th week intrauterine fetal atrophy and mild features of DD; in autopsy no congenital defects detected.
  01-N-
q21/1-1
n.a./
prenatal
AF de novo 47,+mar[?] r(1)(::q21q22::)  centromeric probes; SKY? see below {37} case 1 {52}  

Intrauterine fetal atrophy in week 24; TOP; autopsy confirmed mild intra-uterine growth retardation

  01-N-
q23/1-1
see McCl-01-N-q23/1-1   {23; 31; 36; 52}  
  01-N-
qt23~24/
1-1
female/
2.5y
PBL/
bone marrow
de novo
acquired
51,XX,
+8,+8,+21,+21,+mar 
inv dup(1)qterq23~24:
:q23~24
q43qter)
M-FISH, MCB see below {71}  

normal girl suffering from AML-M5a at age of 2 y --> for larger neocentric marker in non-Hodgkin lymphoma see Ref {72}

 
01-N-
q32/
1-1
female/
9m
PBL de novo 47,XX,del(1q32),+mar(:1q32→qter)
possibly inv dup
n.a. n.a.  see below {28; 52}  
At month 3 of pregnancy mother had a virus infection; at month 6 she was treated for abortus imminens; birth at end of month 8; w: 1900g, l: 43cm, respiratory distress, failure to thrive; At 9m MR, congenital hydrocephalus, VSD, abnormal immunoglobulin.
  01-N-
q43/
1-1
male/
prenatal
AF de novo 47,XY,+mar[50%]/
46,XY[50%]
r(1)(::q43q44::) midi, 11 centromeric probes;  see below {27} case 1; {40} case 13 {31; 36; 52; 80}  

Advanced maternal age and anxiety; no ultrasound abnormalities; birth by cesarean section, due to cardiac rhythm disturbances; child normal at 6m

                     

 

N-Cases with similar imbalances NOT caused by sSMC (N-IMB):

 

                   
  case no.  gender/ age at diagnosis studied 
material
de novo/ 
inherited
GTG-banding result and FISH result incl. grade of mosaicism test
methods
clinical symptoms reference  
  01-N-
IMB-
q32/
1-1
male/
postnatal, infant
AF de novo 46,XY,dup(1)(q32q44) different FISH-probes CGH   {60}  
  01-N-
IMB-
q32/
1-2 to
1-11
further comparable cases
- for review see {61}
{61}  
  01-N-
IMB-
q32/
2-1
female/
postnatal, infant
PBL de novo 46,XX,trp(1)(q32q44) different FISH-probes; array-CGH   {68}