FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 10 -

           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 10   maternal   paternal   unclear


the probably non-dosage sensitive pericentric region of chromosome 10

 


SCHEMATIC CYTOGENETIC DEPICTION                    
  sSMC-10DISCLAIMER

 


 

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 34.46 ---  34.75 uncritical region   [38.80 centromere 42.10]   uncritical region 43.82 --- ? critical region

Below adapted for UCSC hg19, 2009

 critical region 34.43 ---  34.72 uncritical region   [38.00 centromere 42.30]   uncritical region 44.51 --- ? critical region

 DISCLAIMER

 


 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

10p - proximal

10q - proximal

symptoms

developmental delay

38 % 0 %

dysmorphic face

50 %
0 %

finger or toe/foot malformations

29 % 0 %

growth retardation

50 %
0 %

heart defect

50 % 0 %

hypotonia

38 % 0 %

joint problems

25 % 0 %

mental retardation

38 % 0 %

overgrowth

0 % (100%)

urethral problems

50 % 0 %
number of cases (marked with “°” below) 8
1


 


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  
  10-O-
p12.1/
1-1

female/
prenatal

AF de novo 47,XX,+mar[7]/
46,XX[8]
min(10)(:p12.1q11.22:)
FI
SH-data: RP11-232C13 (36.23 MB) and RP11-178A10  (42.32) on sSMC
cenM,
subcenM
see below {38} case 1
{23} case 60
 

abnormal second trimester screen (AFP3) with DS risk of 1/31; family history unremarkable; US normal in week 19; AFP normal; delivery by cesarean section for fetal distress at 40 weekgestation. Birth weight was 8 lbs 1 oz length 20 1/2 inches. normal newborn. normal at 1 year of age, At 1 year, ready to walk (currently walking holding on to furniture), drinks from a cup, has a neat pincer, saya mama, dada. Her weight is 20 lbs 8 oz and she is 31 inches long.

  10-O-
p11.23~
11.22/
1-1

female/
prenatal

AF de novo 47,XX,+mar[16]/
46,XX[8]
min(10)(:p11.23q11.1~11.21:)*
FISH-data: CTD-2130I7 (30.8 MB) and RP11-79K19  (33.5 MB) on sSMC;
array-data size: 36.2MB-42.9Mb
SKY, BACs; oligo array-CGH amniocentesis due to pregnancy after ovarian hyper stimulation;  normal child born {39}  
  10-O-
p11.21~
11.22/
1-1

female/
prenatal

AF de novo 47,XX,+mar[100%] r(10)(::p11.21~11.22q
11.21~q11.22::)
FISH-data: RP11-232C13 (36.23 MB) and RP11-178A10  (42.32) on sSMC
cenM;
subcenM; UPD-test
advanced maternal age, ultrasound normal, normal child born {38} case 2  
  10-O-
p11.21/
1-1

female/
prenatal

AF de novo 47,XX,+mar[80]/
46,XX[20]
min(10)(:p11.21q11.22:) cenM;
subcenM
advanced maternal age, ultrasound normal, normal child born in week 33 by section; birth weight 2100g {38} case 3  
  ***
10-O-
p11.21/
2-1
***

male/
prenatal

AF de novo 47,XY,+mar[15]/
46,XY[35]
r(10)(::p11.21q11.21::)
34.40- 44.45 MB {38}
34.75-43.82 MB {0}
centromeric probes;
subcenM;
array-CGH
marker detected prenatally, normal child born, at age of 10y normal {0}
{38} case 4
 
  10-O-
p11.21/
3-1
female/
prenatal
AF de novo 47,XX,+mar[25]/
46,XX[5]
min(10)(:p11.21q11.21:) cenM;
subcenM
normal child born {42} case 2; {47} case 2
 
  10-O-
p11.1/
1-1

female/
prenatal

AF de novo 47,XX,+mar[50%]/
46,XX[50%]
min(10) (:p11.1q11.21~q11.22:)
FISH-data: RP11-178A10  (42.32) on sSMC
cenM,
subcenM
see below {38}case 5  

normal in ultrasound; twin pregnancy, karyotype of brother normal; birth weight of female with marker 2280g and of male 2350g; both at 8w normal

  10-O-
p11.1/
2-1

female/
prenatal

AF de novo 47,XX,+mar[100%] min(10)(:p11.1q11.1:) or min(10)(:p11.1q11.1:
:p11.1→q11.1:)
centromeric probes,
subcenM; UPD-test
see below {38} case 6  

Amniocentesis due to advanced maternal age;  twin pregnancy, karyotype of brother normal; normal babies born; female with mar normal at 2y

                     

 

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  
  10-O-
IMB-
p11.1/
1-1
 male/
prenatal
AF paternal 46,XY,psu dic(10)(pterq11.22::p11.1qter) subcenM amniocentesis due to psychological reasons  {38} case 7  
                   

 

O-cases with unclear/insufficient characterization of the sSMC itself (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  
 

10-
CO-1

female/
prenatal

AF de novo 47,XX,+mar[?%]/
46,XX[?%]
mar(10) SKY, cep 10 maternal serum Down syndrome screening test gave high risk value; child born and normal at 2 years {37} case 12  
                     

 


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  
  10-W-
p15/
1-1   °
female/
9m
PBL de novo 47,XX,+mar[35%]/
46,XX[65%]
r(10)(::p15q11.1::) wcp, cep see below {21}  
growth retardation, global developmental delay, mental retardation, hypotonia, dolichocephaly, hypertelorism, down turned corners of the mouth, prominent cheeks, flat nasal root, micrognathia, severe joint
  10-W-
p15.3/
1-1
female/
10y
PBL n.a. 47,XX,+mar[9]/
46,XX[56]
r(10)(::p15.3q11.22::) cep probes; subcenM-FISH, MCB see below {0} provided by Jason Anderson,
Brisbane, Australia
 
mild intrauterine growth retardation in the last trimester; postnatal: initial feeding problems; later intellectual impairment; bilateral talipes equinovarus, slightly different facial features; OFC, height and weight described as average; slightly flat midface and rather prominent large ears;
  10-W-
p15.3/
1-2  °
female/
1w
PBL/
Fibro
de novo 47,XX,+mar[100%] min(10)(p15.3q10:)* n.a. see below {20}  
hypotonia, ventricular septal defect, right sided renal agenesis, dolichocephaly, wide sutures, upswept frontal hair-pattern, broad nasal root, inverted boarder of the lips, short neck, hypoplastic nails, bilateral talipes equinovarus
  10-W-
p15.3/
1-3  °
female/
1w
PBL mat
(karytype of mother: 47,XX,-10,+fis(10)(p10),+fis(10)(q10)
47,XX,+mar[100%] min(10)(p15.3q10:)* wcp 10, cep 10 see below {43}  
in pregnancy IUGR and oligohydramnios, birth weight 2,400 g (5th centile), length 47 cm (10th centile),  head circumference of 33 cm (10th centile). neonatal : craniofacial dysmorphisms like: dolichocephaly with wide sutures/fontanelles,  elongated face, high frontal hairline, hypertelorism, large ears, bilateral cleft lip and palate,  apparently wide and flat nasal bridge, prominent cheeks. At 4 months: microcephaly, barrel shaped chest, marbled skin, secundum atrial septal defect (ASD), flexion contractures of large joints, and clubfoot anomaly, generalized hypotonia, growth and developmental delay. At12 months global developmental delay was established.
  10-W-
p12/
1-1  °
male/
15y
PBL n.a. 47,XY,+r[19%]/
46,XY[10%]
r(10)(::p12q10::) midi
FISH:D10Z1; UPD-test
see below {2} case M
{3}
 
mild mental retardation, pre- and post-natal growth retardation, cleft lip and palate, and mild facial dysmorphism
  10-W-
p11.23/
1-1
see McCl-10-W-p11.23/1-1   {6-15; 17; 22}  
   
10-W-
p11.23/
1-2
female/
prenatal
AF de novo 47,XX,+mar[3]/
46,XX[7]
min(10) (::p11.23→q11.21::)*
~6.9 MB in p and ~0.7 MB in q in euchromatin
pericentric BAC-set ? AMA, then pre term delivery; failure to thirve, dysmorphsim, neonatal hypotonia {46} case 4  
  10-W-
p11.22/
1-1    °
female/
1y
PBL de novo 47,XX,+mar[15]/
46,XX[5]
min(10) (::p11.2q11.1::)*
31.65-38.70 MB
array-CGH see below {40} case P-6  
urogenital abnormalities, left hypoplastic kidney, vaginal atresia 
 
  ***
10-W-
p11.22/
1-2   °
***
male/
prenatal
AF n.a.  47,XY,+mar[5]/
46,XY[19]
min(10) (::p11.22q11.1::)*
aCGH: 34.46-38.69
array-CGH Advanced maternal age; born with tetralogy of Fallot {44} case 11
 
 
  10-W-
p11.22/
2-1
    °
female/
prenatal
AF n.a.
 
47,XX,+mar[19]/
46,XX[56]
min(10) (::p11.22q11.1::)*
aCGH: 31.65-38.69
array-CGH horseshoe
kidney
{44} case 12  
  10-W-
p11.2/
1-1  °
female/
12y
PBL/oral mucosa de novo 47,XX,+mar[8]/
46,XX[48] in PBL (in OM sSMC in 16%)
r(10) (::p11.2q11.1::)* midi, wcp 10, cep 10 , UPD-tzest see below {19}   
uneventful pregnancy; birth length 51 cm and weight 3120 g. At 6 months thrombocytopenia. At 12 y admission diagnose sex chromosome aberration: length 132.5 cm (2 cm below the 3rd centile), weight 25.8 kg (4 kg below the 3rd centile), skeletal age ~2 y delayed; no signs of puberty. IGF1 levels decreased, growth hormone levels in normal range. normal intelligence, but attention deficit disorder.
  10-W-
p11/
1-1  °
female/
prenatal
AF/PBL de novo 47,XX,+mar[24]/
46,XX[26] in PBL (in AF 13:15)
min(10) (:p11.1q11.2:)*
FISH-data: RP11-178A10  (42.32) on sSMC
subcenM see below {18}   
at 1y height 90-95th centile, other values normal; at 2y oral dyspraxia
                     

 

 


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  
  10-W-
IMB-
p13/
1-1
 female/
21y
PBL de novo 46,XX,dup(10)(p11p13) n.a. see below {32}  

severely mentally retarded, autistic and aggressive behavior, minor dysmorphism, skin syndactyly of fingers and toes

  10-W-
IMB-
p13/
2-1
 female/
4y
PBL de novo 46,XX,dup(10)(p11p13) n.a. conductive deafness, minor anomalies, mental retardation {33}  
  10-W-
IMB-
q11.1/
1-1 to
7-1
 male and female/
postnatal
PBL de novo 46,dup(10)(q11.1q22) or
46,
dup(10)(q21q22)
wcp 10 see below {27}see also {34}  

mild to moderate developmental delay, postnatal growth retardation, microcephaly, prominent forehead, small and deep set eyes, epicanthus, upturned nose, bow shaped mouth, micrognathia, thick and flat helices of the ears, and long, slender limbs. Severe ocular malformations are possibly part of the syndrome

  10-W-
IMB-
q11.1/
8-1
 male/
postnatal
PBL de novo 46,dup(10)(q11.1q11.21)
aCGH: 46.57-51.26Mb
aCGH see below {41} patient 2  

corpus callosum hypoplasia, mild dilatation of subarachnoid areas and frontotemporal atrophy, severe central hypotonia, ataxia, triangular face, enlarged cranium cerebrale, bifid scrotum, cryptorchidism, ulnar deviation of both elbows, deep palmar creases of hands and feet and syndactyly of 2nd and 3rd toes bilaterally.

  10-W-
IMB-
q11.2/
1-1
 male/
at birth
PBL de novo 46,XY,dup(10)(q11.2q22.3) n.a. see below {30}  

birth weight after 42 weeks of gestation 2890g. clubfeet, retroflection of the head, laryngeal stridor, ASD, slight monolateral pyelectasy and dysmorphism. At 2 months bronchiolitis. At four months failure to thrive, moderate hypotonia.

                   

 

 


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  
  10-
U-1
male/
prenatal
AF de novo 47,XY,+mar[11]/
46,XY[11]
i(10)(:p11.1q11.1:
:p
.or.q11.1q11.1 or p11.1)[15]/
i(10)(pter
q11.21:
:q11.21
pter)x2 (tetraploidmitosis)[2]/
min(18)(p11.1
q11.1)[3] 
cenM;
subcenM
singularly umbilical cord artery, complex heart defect and microcephalus detected in ultrasound; fetus spontaneously aborted {1} case 35  
  10-
U-2
female/
prenatal
CH/AF/ fibroblasts de novo 47,XX,+mar[15]/
46,XX[2]
AF: 17:3; Fibroblasts: 4:6
min(10)(:p12.31q11.1:)
maternal UPD 10
midi, UPD-test see below {16, 45}  

amniocentesis due to advanced maternal age; twin of patient was death at 13 weeks of gestation; no abnormalities in patient in ultrasound; pregnancy terminated in week 18; no abnormalities in autopsy

  10-
U-3
n.a./
prenatal
AF n.a. 47,+mar[?%] mar(10) SKY no info available {25} 1 new case  
  10-
U-4
n.a./
prenatal
AF mother has balanced rearrangement (involved. chr. 10) 47,+mar[100%] mar(10) wcp 10, cep 10   {36}case 7  

sonographic malformations; Bilateral pyelectasy short femurs, clubfeet, pleural effusion; fetopathology: facial dysmorphism: hypertelorism, microphthalmos, low-set ears, microretrognathism, cleft palate, short femurs, clenched hands, clubfeet; pyelectasy

                     

 


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  
  10-N-
pt15~
14/
1-1
male/
prenatal
AF de novo 47,XY,+mar[100%] inv dup (10)(pterp15~14:
:p15~14
pter) 
CGH; subtelomere probes 10p and 10q see below {5; 17; 22; 26}  
Amniocentesis due to advanced maternal age; normal in ultrasound; pregnancy terminated; no abnormalities in necropsy
  10-N-
q11/
1-1
see McCl-10-N-q11/1-1 {4} case 8
{14; 17; 22; 26}
 
                     

 

other neocentromere 10 cases (no sSMC):

Voullaire LE, Slater HR, Petrovic V, Choo KH.
A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: activation of a latent centromere?
Am J Hum Genet. 1993 Jun;52(6):1153-1163.     → see as well above case W-p11.23

 

 

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  
  10-N-
IMB-
p14/
1-1
female/
newborn
PBL de novo 46,XX,der(6)t(6;10)(p25;p14) CGH, wcp 6, wcp 10 see below {24}  
Born after uneventful twin pregnancy of 37 weeks. Delivery by cesarean section. Birth weight 2630 g, length 46 cm, and head circumference 34cm. Her twin, a boy, did not present with any anomaly. She showed hypotonia and for faintness after a meal, a mild facial dysmorphic, associating hypertelorism and upslanting palpebral fissures. The skin and hair were pale and blond, respectively, while the parents, had a matt complexion. Magnetic resonance imaging (MRI) of the head showed a corpus callosum agenesis. The difficulty in eating and a gastro esophageal reflux were due to a glottis stenosis. Development at 8 months was delayed. She was 63 cm tall and weighed 6100 g (<2 SD), head circumference was normal at 44.5 cm. An important psychomotor retardation was noted. There was significant hypotonia. At this age, craniofacial dysmorphic was evident, including hypertelorism, a large nose, a pronounced philtrum, thin lips and low set ears, an abnormal pallor compared to her family.
  10-N-
IMB-
p14/
add. cases
see {31} {31}  
  10-N-
IMB-
q24/
1-1
female/
11y
PBL de novo 46,XX,dup or trp(10)(q26qter) YAC probes see below {28}  
Fetal movements reduced during pregnancy. Born at term, birth weight of 3800 g (50th-75th centile), length 50 cm (25th-50th centile), head circumference 35 cm (25th-50th centile). Mild distal arthrogryposis of the hands. Development delayed; walked at 20 months, is first words at 5 years. At 11 years 8 months, weight 35.2 kg (25th-50th centile), length 153 cm (75th-97th centile), head circumference 53.8 cm (50th-75th centile). Minor facial anomalies, with midface hypoplasia, flattened forehead with a high anterior hairline, central anterior cowlick, and narrow palpebral fissures. Outer canthal distance 9.3 cm (75th centile), inner canthal distance 3.1 cm (50th-75th centile). Ears prominent with poorly folded helices. Hypertrophic gingival, ventral placement of the maxillary canine teeth. A large gap between first and second toes. Hypotonic with open mouth and reduced facial expression, hypermobile elbow joints, high, arched palate, and a lumbar scoliosis. Distal arthrogryposis of the hands with flexion contractures at the proximal interphalangeal joints of the second to fifth fingers. The thumbs showed absence of flexion at the metacarpophalangeal joints. He has moderate mental retardation, with an intelligence quotient of 46 on the Terman scale, at the age of 5.5 years.
  10-N-
IMB-
q26/
1-1 to
1-3
5 cases with trisomy 10qter
see also {34}
{29} 5 cases