FISH

SMALL SUPERNUMERARY MARKER CHROMOSOMES

- sSMC 19 -

           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 19   maternal   paternal   unclear


the probably non-dosage sensitive pericentric region of chromosome 19

 


SCHEMATIC CYTOGENETIC DEPICTION                    
  sSMC-19DISCLAIMER

 


 

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 ? --- 17.50 uncritical region   [26.70 centromere 30.20]   uncritical region 43.88 --- ? critical region

Below adapted for UCSC hg19, 2009

 critical region ? --- 15.20 uncritical region   [24.40 centromere 28.60]   uncritical region 39.08 --- ? critical region

 DISCLAIMER

 


 Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

19p - proximal

19q - proximal

symptoms

autism

- 13 %

brain malformations

- 13 %

developmental delay

(100 %) 100 %

dysmorphic face

- 50 %

heart defect

- 13 %

hypotonia

- 25 %

mental retardation

- 38 %

microcephaly

- 13 %

obesity

- 13 %

overgrowth

- 13 %

vision impaired

- 13 %
number of cases (marked with “°” below) 1 8


 


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  
  19-O-
p13.11/
1-1
female/
prenatal
AF
(EKF-
cellbank)
de novo 47,XX,+mar[64]/
46,XX[24]
min(19)(:p13.11q11~12:) 
FISH-data: RP11-22G10 (22.98MB) on sSM
C
cenM; subcenM, UPD-test Amniocentesis due to advanced maternal age; normal child, APGAR 9/10/10; weight 3720g, length 54 cm; OFC 35.5 cm; at two years normal and well developed (U7 was normal) {0} provided by Dr. Pruggmeyer, Peine, Germany  
  19-O-
p13.11/
2-1
male/
prenatal
AF de novo 47,XY,+mar[10-15%]/
46,XX[85-90%]
min(19)(:p13.11q12:)[2]/
min(19)(:p12
q12:)[1]
cenM; M-FISH, subcenM Advanced maternal age; ultrasound normal; normal child born {0} provided by Dr. Gerresheim, Bochum, Germany  
  ***
19-O-
p13.11/
3-1
***
female/
28y
PBL
(EKF-
cellbank)
de novo 47,XX,+mar[60%]/
46,XX[40%]
min(19)(:p13.11q11:)[3]/
r(19)(::p13.11
q11::)[9]/
r(19)(::p13.11
q11:
:p13.11
q11::)[2]
FISH-data: RP11-22G10 (22.98MB) on sSM
C
aCGH: 17.50-33.59
midi; MCB; subcenM;
array-CGH
normal female {52}  case Srm-3  
  19-O-
p13.11/
4-1
female/
43y
PBL n.a. 47,XX,der(7)inv(7)(p22q36)inv(7)(q31.2q36),+mar[15]/
46,XX,der(7)inv(7)(p22q36)inv(7)(q31.2q36)[67]
r(19)(:p13.1q11:) locus spec. probes, array-CGH normal female, detected due to clin. abnormal daughter {43}  
  19-O-
p13.11/
5-1
female/
adult
PBL n.a. 47,XX,+mar[8]/
46,XX[7]
47,XX,+min(19)(:p13.11q12:)[3]/
47,XX,+min(19)(:q13.11
p12: :p12q13.11:)[2]/
47,XX,+min(19)(:p12
q13.11:)[2]/
47,XX,+min(19)(:p13.11
q12: :q12p13.11:)[1]/
46,XX[7]
cenM;  subcenM normal female, pregnant {0} provided by Dr. D. Čemerlić, Subotica,
Serbia
 
  19-O-
p12/
1-1
male/
3y
PBL
cell line at ECACC DD0817
de novo 47,XY,+mar[90%]/
46,XY[10%]
r(19)(::p12q12::) FISH with all available centromeric probes, cernM, subcenM, MCB; UPD test only for #16 Amniocentesis due to advanced  maternal age; clinically normal at 17m {2} case 16
{18} case 9
{19} case 8
 
  ***
19-O-
p11/
1-1
***
female/
31y
PBL
(EKF-
cellbank)
n.a. 47,XX,+mar[25]/
46,XX[75]
min(19)(:p11.1q13.1:)
FISH-d
ata: RP11-14D17 (36.90MB) on sSMC
aCGH: 32,981,858-43,889,713 MB
cenM; subcenM;
aCGH
genital hypoplasia {23}case 12  
                     

 

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  
  19-
CO-1
male/
prenatal
AF de novo 47,XY,+mar[?]/
46,XY[?]
r(19) different FISH probes (cep1/5/19; wcp 19) normal {3} case 17
{4} case 5
 
  19-
CO-2
male/
prenatal
AF
PBL
de novo 47,XY,+r[29]/
46,XY[21]
r present in
46%of PBL
r(19) all centromeric probes amniocentesis due to advanced  maternal age. normal at age of 18m.  {6} case 2  
  19-
CO-3
female/
prenatal
AF
PBL
de novo 47,XX,+mar[14]/
46,XX[8]
r present in
46%of PBL
?r(19)(::p11~13.1
q11~13.1::)*
centromeric probes, wcp 1, 5, 19 amniocentesis due to advanced  maternal age. normal at age of 3y.  {16} case 15  
  19-
CO-4
female/
adult
PBL n.a. 47,XX,+mar[?100%] mar(19) n.a. normal female; mar detected due to mar presence in unborn child. {20} mother of case 74  
  19-
CO-5
female/
prenata
AF n.a. 47,XX,+mar[3]/
46,XX[16]
mar(19) wcp 19 normal child born [53} case 22  
                     

 


References

Cases with clinical findings (W)

N.B. paper below cited in {45} as sSMC(19) case has indeed a karyotype 46,XX,r(19)!!
Flejter WL, Finlinson D, Root S, Nguyen W, Brothman AR, Viskochil D. Familial ring (19) chromosome mosaicism: case report and review. Am J Med Genet. 1996 Dec 18;66(3):276-80.

 

                     
  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  
  19-W-
pter/
1-1
male/
3 m
PBL de novo 47,XY,+mar[52]/
46,XY[48]
min(19)(pterp11)* all centromeric probes; different YAC-probes see below {24; 29}  
normal directly after birth, ( 3550g, 51cm, OFC 36cm, Apgar 9/10);  gastrooesophagial reflux at 24 days; sonography of brain normal; at 3 m generalized muscular hypotonia; at 7.5-9y: severe  muscular hypotonia, severe mental retardation, developmental delay, dysmorphic features, strabismus, low set ears, clinodactyly, seizures, epilepsy, no walking;
  19-W-
pter/
1-2
male/
12 year
PBL de novo 47,XY,+mar[75]/
46,XY[25]
mar(19)(pterp11::)* all centromeric probes; wcp 19, pcp 19p similar to case 19-W-pter/1-1 {29 - case 2}  
  19-W-
p13.1/
1-1
female/
prenatal
AF de novo 47,XX,+mar[38]/
46,XX[17]
r(19)(::p13.11
q13.11~13.12::)[16]/
r(19;19)(::p13.11

q13.11~13.12:
:p13.11
q13.11~
13.12::)[2]/
min(19)(:p13.11
q13.11~
13.12:)[5]
cenM;
subcenM
see below {17} case 19-4  
advanced  maternal age; no ultrasound abnormalities apart from growth retardation (1 week delayed) and the nasal bone was not visible; pregnancy ended with spontaneous abortion - no heart activity in gestational week 14+4
  19-W-
p13.1/
1-2
female/
newborn
PBL; skin fibroblasts de novo 47,XX,+mar[5]/
46,XX[15]
r(19)(::p13.1q13.1::) midi, wcp 19, cep 1/5/19 see below {38} case 1  
Born after normal pregnancy; intractable seizures on the first day of life. Also acquired microcephaly, severe developmental delay, a seizure disorder, and marked visual impairment. At 3y acquired microcephaly; head circumference 44 cm (<3rd centile), height 89 cm (10%), weight 13.1 kg (25%). No dysmorphic features, no organomegaly, with normal skin and extremities. Neurological examination: profound cognitive and gross motor impairment; no persistent primitive reflexes an overall developmental age of less than 4 months; normal routine blood work and cerebrospinal fluid analysis; ophthalmologic exam: optic atrophy, poor vision, and optical oscillation. Somatosensory evoked potential, brainstem auditory evoked potential, and peripheral nerve conduction were normal. Head MRI showed diffuse hyperintensity on T2-weighed images early on but there was interval maturation of myelination with only mild delay in myelination at age 3 years. There was under-operculation with simplification of the gyri in the frontal lobe, and thin corpus callosum suggesting cerebral dysgenesis. Bone films of spine showed thoraco-lumbar scoliosis.
  19-W-
p13.1/
2-1
male/
prenatal
AF; PBL; de novo 47,XY,+mar[100%] min(19)(pterp13.3: :19p13.119q13.1:)* WCP multiprobe device; midi; subtel 19 see below {38} case 2  
Born by cesarean section at 37 weeks gestation as twin B of a dichorionic, diamniotic pregnancy. Twin A was a healthy male; 46,XY. The pregnancy was complicated by gestational diabetes, and ultrasound diagnosis of a left diaphragmatic hernia, probable ventricular septal defect, and small lung volume. APGAR scores were 4, 6,and 5. Birth weight 2,300 g (10th centile). Potsnatal: severe hypoxemia secondary to the diaphragmatic hernia. Echocardiogram: patent foramen ovale and tricuspid regurgitation. Abdominal ultrasound: rotated, echogenic right kidney and ectopic left kidney. Vision and hearing evaluations were normal. Other complications in the newborn period included placement of a G-tube and Nissen fundoplication for feeding aversion problems, laparoscopic repair of a small bowel obstruction, and frenotomy for treatment of tongue tie. At eight months: interactive child with microcephaly and significant delays in development. Height 62.5 cm (<3rd centile), weight 5.9 kg (<3rd centile), head circumference 39.75 cm (<3rd centile); central hypotonia, midface hypoplasia, and protuberant ears. At 2 years cognitive skills at approximately the 12-month level and motor skills at the 10-month level. Height 74.5 cm (<3rd centile), weight 9.4 kg (<3rd centile), head circumference 43.5cm(<3rd centile); moderate thoracic scoliosis and central hypotonia; still exhibited significant feeding aversion.
  19-W-
p13.1/
3-1  °
male/
5 year
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[19]/
46,XY[11]
min(19)(:p13.11~13.12q12:) cenM;
subcenM
developmental delay {0} provided by Dr. Belitz  Berlin,  Germany  
  19-W-
p12/
1-1
male/
1 w
PBL de novo 48,XY,+marx2[100%] min(19)(:p12q12:)x2 cenM;
subcenM
see below {27}case 30  
 full term pregnancy (G4,P2; G2 miscarriage, G3, legal abortion) at birth weight 2800g, lenght 49cm, OFC 34cm; (OFC at 11m 43cm) facial dysmorphism, hypertelorism, low set dysmorphic ears, preauricular fistula, high palate, flat wide root of the short nose; flat round face, narrow palpebral fissures, microretrognathia, long philtrum, open mouth, high line of hair, spars hair spare eyebrows, horizontal fissures, epicanthus, systolic murmur, heart defect, severe muscular hypotonia, decreased reflexes, short neck, mild lymphoedema at hand and feet, pes planus, ventriculomegalia, severe developmental delay, small scrotum, cryptorchidism
  ***
19-W-
p12/
2-1
***
male/
3 m
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[60-90%]/
46,XY[40-10%]
min(19)(:p12q12:)
size in p 2.59MB (= position 25.91 MB) , in q 2.3 MB (= position 32.4MB)
MCB;
subcenM
midi, array-CGH (Agilent 244k-chip)
see below {0}provided by Dr. Altus, Magdeburg, Germany
{26}
 
 born in week 31 spontaneously, weight 2060g (93centile), length 42,5cm (58 centile), OFC 31.5 cm (92 centile) , APGAR 7/8/8hyperbilirubinamia, subluxation of hip joint, Pes calcaneovalgus congenitus, periodic breathing, stridor cong, feeding problems. at 3 months: extreme restlessness, nearly opstotone posture; OFC now at 10. centile; at 5m: hyperexitability, developmental delay
  19-W-
p12/
3-1
male/
16y 8 m
PBL n.a. 47,XY,+r1[?%]/
47,XY,+r2[?%]
r(19)(::p1?2q11::)*/
r(19)(::p11
q1?2::)*
cep probes wcp 19, centromere near cosmids see below {28}  
overweight, mentally retarded with macrocephaly, hypertelorism, antimongoloid slants, epilepsy (convulsive seizures with or without hyperthermia from 1y)
  19-W-
p12/
4-1
female/
15y
PBL de novo 47,XX,+r[100%] r(19)(::p12q12::)
aCGH: 23.12-33.29MB
M-FISH, diff. FISH-probes, aCGH see below {45}  
As newborn child seemed normal. Later in childhood, developmental delay, particularly of language skills. At 15y height >95th centile, high forehead, down-slanting palpebral fissures, wide diastema between upper incisors, high palate, short fraenulum of the upper lip, prominent lips and scoliosis, long and tapering fingers, fifth finger campodactyly, hallux valgus, fifth toe clinodactyly, pes planus. Overall neuropsychological picture: borderline intelligence with specific cognitive deficits in the processing of verbal information as well as learning disorders. Brain magnetic resonance imaging: enlarged cisterna magna with slight hypoplasia of the basal part of the cerebellar hemispheres as well as of the inferior vermis; the posterior fossa was normal.
  ***
19-W-
p12/
5-1  °
***
male/
13y
PBL
(EKF-
cellbank)
de novo 47,XY,+mar[23]/
46,XY[7]
min(19)(:p12q13.11~13.12:)
size in
p: RP11-22G10 in subcenM present on sSMC (22.98 MB - no signal in p on array), in q according to array: sSMC goes to 36.3 MB
cep; wcp;
subcenM; array-CGH
see below {0} provided by Drs. Prager and Junge, Dresden, Germany  
Normal pregnancy and birth. At birth weight 4080g, length 52cm, APGAR 9/10; OFC 37cm; sitting with 6 months, walking with 13 months, speaking with 3 years. Developmental delay noticed from ~5 years. Anxious and impulsive behavior,
  19-W-
p12/
5-2  °
male/
4y
PBL
(EKF-
cellbank)
n.a. 47,XY,+mar[50%]/
46,XY[50%]
min(19)(:p12q13.1?1:) cenM;
subcenM
developmental delay {0} provided by Dr. Albrecht, Essen, Germany  
  19-W-
p12/
5-3  °
male/
4y 10m
PBL n.a. 47,XY,+mar[44-60%]/46,XY[54-40%] mar(19)(:p12q13.11:)
positions: 19.80 to 38.21
aCGH see below {41;44}  
normal pregnancy apart from oligoamnion in last month. weight length and APGAR normal at birth; Asperger syndrome = autism; mild hypotonia; milestones in development delayed
  19-W-
p12/
6-1
female/
7y
PBL n.a. 47,XX,+r[3]/46,XX[7] r(19)(::p12q13.2::)
aCGH: 23.73 to 43.47
different FISH-probes; aCGH global developmental delay {46} case 11  
  19-W-
p11/
1-1  °
male/
5y
PBL de novo 47,XY,+mar[?]/
46,XY[?]
min(19)(:p11q13.11:)
FISH-data:
26.7-at least to 33.3MB
cenM;
subcenM
see below {17} case 19-1  
Pre- and postnatally no clinical signs before the age of 1.5 years; then slight developmental retardation: first speech with 18 months; walking with 22 months; weight: 8.82kg (1.5y); height 81cm (1.5y); head circumference 49.7cm (1.5y); minimal cerebral dysfunction (MCD) at age of 4; no severe clinical signs.
  19-W-
p11/
1-2  °
n.a./
2y
PBL de novo 47,+mar[100%] min(19)(:p11q13.11:)*
size  ~0.4MB
n.a.; subcenM with 3 BACs; array CGH see below {25} case 20  
Metopic craniosynostosis; ventricular septal defect (VSD); strabismus; significant developmental delay; not rolling or sitting at 7 months of age; “not talking” at 27 months of age.
  19-W-
p11/
2-1  °
female/
4.5y
PBL de novo 47,XX,+r[30%]/
46,XX[60%]
r(19)(::p11q13.32::)
aCGH: no euchromatin detected
midi;
aCGH
see below {0} provided by Dr. Zvi Borochowitz; Israel  
severely affected with mental retardation, microcephaly and dysmorphic features including small ears, anti-mongolian slant, broad faces, bulbous nose, large cheeks and somewhat furrowed forehead
  19-W-
p11/
3-1
male/
postnatal
PBL de novo 47,XX,+mar[30] der(19)(:p11q11::q12q13.2:
:q13.2
q13.31:)
aCGH: 30.74-36.12 and 42.89-43.92
aCGH autsim, DD, dysmorphic face, obesity, friendly personality {51} case 8  
  19-W-
p1?0/
1-1   °
female/
49y
PBL n.a. 47,XX,+r[7]/
46,XX[18]
r(19)(::p1?0q13.42::)* CGH; cep1/5/19; wcp 19; pcp19p, pcp19q, subtel  19q see below {5}  
walking at age of 2y, speech at 4-5y; residential care since age of 16y.  At age of 71y height of 132 cm, head circumference of 52.5 cm, blood pressure of 180/110 mm Hg, poor peripheral circulation, earIy hypertensive changes in both optic fundi, poor vision, Upward slanting palpebral fissures, large tongue, protruding lower lip, normal pa1mar creases, normal female genitalia, and deep set toe nails; radiological signs of subluxed, osteoarthritic hip joints. Moderate to mild learning disability.  
  19-W-
p10/
2-1
see McCl-19-W-p10/1-1   {7}  
  19-W-
p10/
3-1  °
male/
14y
PBL de novo 47,XY,+mar[100%] r(19)(::p10q13.2::)* M-FISH cep probes; CGH see below {22}  
Born at 39 weeks gestation after a pregnancy with gestational diabetes and a delivery reported to be prolonged; birth weight was 3950g. Hypertonia was noticed from birth and continued throughout the first 6 months of life; Significant for motor and cognitive developmental delay identified from early infancy. At 31, 36 and 60 months of age he had the developmental age of 18, 20 and 30 months, respectively. He gained speech skills at 6 years of age and currently, his cognitive skills are very limited, with poor learning and speech abilities; limited social interactions; mild dysmorphic features including macrocranium, round face, upslanting eyes and thick auricles Brain CT and MRI performed revealed cortical atrophy, partial agenesis of the corpus callosum and mild changes in the white matter in the occipital lobes; several generalized tonic-clonic seizures started at 1 year of age. EEG and video-EEG performed at the first and third years of life showed waves and spikes from foci in both hemispheres with a few generalized bursts, and slow background activity. Growth pattern was characterized by height at the 50th percentile over the first 2 years of life and along the 90th percentile thereafter, with head circumference at the 90th percentile from infancy; most prominent growth feature was a remarkable weight gain: BMI 33.5, 44, 46 and 51 at 5, 8, 10 and 12 years of age, respectively. Subsequent to morbid obesity, he developed several co-morbidities:(1) hypercholesterolemia (2) moderate elevations in liver transaminase levels, (3) hyperuricemia that responded to a short-term treatment with allopurinol; (4) a mild degree of pulmonary hypertension, documented by echocardiography; and (5) Pickwickian syndrome, manifested by night snoring, daytime somnolence and episodes of sleep apnea. At about 13 years of age the patient started pubertal maturation, and currently (at 14 years of age) he is in Tanner pubertal stage.
                     

 

 

 

W-cases with unclear/insufficient characterization of the sSMC itself (CW)

 

                     
  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  
  19-
CW-1
female/
5y
PBL de novo 47,XX,+mar[36]/
46,XX[54]
r(19)  FISH probe  wcp 19 see below {12}  
Normal pregnancy and birth; weight: 4870g, length 55g, OFC 37.5g →all >95th centile;  At 11m developmental delay; at 0m hypotonia, gross motor delay; at 5y still weight, lenght and OFC  >90. centile; mild dysmorphism including bifronatal narrowing, prominent glabella, deep-set eyes, bulbous nasal nip, prominent lower jaw, short fat hands with long , tapering fingers; mild hypotonia, slightly hunched back; 
  19-
CW-2
female/
0.5y
PBL de novo 47,XX,+mar[60%]/
46,XX[40%]
in both monozygotic twins
mar(19)  FISH probe  wcp 19 see below {13}  
Twins born in week 35 of gestation, mild neonatal jaundice; normal at birth; at 5m twin II had a generalized tonic-clonic seizure associated with fever; at 6m other similar seizures without feaver; at 22m she was found dead in her cot and was presumed to have had a prolonged seizure. 
In Twin I eyelid twitching and flickering at 6m and seizures subsequently. developmental delay occurred and lost of ability to walk unaided at 18m. OFC always on 90. centile; abnormal EEG; developmental delay; died at 4y8m due to a prolonged status epilepticus (4h)
  19-
CW-3
male/
prenatal
AF de novo 47,XY,+mar[27]/
46,XY[23]
r(19)   D1Z7/D5Z2/D19Z3; wcp 19 see below {14} case 3  
Amniocentesis due to abnormalities identified on ultrasound: oligohydramnios, clubfoot and increased nuchal thickness. parents elected to terminate the pregnancy.
  19-
CW-4
female/
1y
PBL de novo 47,XX,+mar[40%]/
46,XX[60%]
r(19p)   M-FISH; D1Z7/D5Z2/D19Z3; wcp 19; pcp19p; pcp19q; sub-telomere 19p 19q12 probe RP11-375D11 see below {15}  
normal pregnancy, at birth weight: 3055g, length 49cm, OFD 33cm; APGAR 5/7; redundant skin, two cavernous angiomas on the back, hypertrophic clitoris, congenital hip dysplasia which required orthopedic correction, cutis marmorata, peripheral cyanosis, joint hyper laxity, axial hypotonia, transient hypocalcemia and hypoglycemia. Att 12 months, no head and trunk control, severely hypotonic, thin hair, high and prominent forehead, round face, sparse eyebrows, downward slanted palpebral fissures, hypertelorism, depressed mid face, low nasal bridge, short nose, anteverted nares, chubby cheeks, long philtrum, protruding tongue, prominent lower lip, receding chin, low-set asymmetric and dysmorphic ears with prominent helix, spaced nipples, and tapering fingers (Fig. 1). Brain MRI disclosed the enlargement of the lateral ventricles with moderate to severe cortical atrophy.
  19-
CW-5
female/
postnatal
PBL n.a. 47XX,+mar[?%] min(19)
44.9 MB size
  array-CGH see below {39} 1 case  
ophthalmologic disease
  19-
CW-6
n.a./
prenatal
AF de novo 47,+mar[?%] r(19) n.a. abnormal sonography; TOP {40} 1 case  
  19-
CW-7
female/
1m
PBL de novo 47,XX,+mar[92]/
46,XX[83]
mar(19)(:p1112:)
mlpa p181x3
MLPA; cep 1/5/19 abnormal facial appearance {0} provided by Dr. A. Delicado Navarro, Spain  
  19-
CW-8
female/
2y
PBL n.a. 47,XX,+r[100%] r(19) SKY multiple congenitals abnromalities {48} case F0628560  
  19-
CW-9
female/
12y
PBL n.a. 47,XX,+mar[100%] min(19) SKY mental retardation {48} case F0642312  
                     

 


 


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  
  19-U-
1
female/
prenatal
AF de novo 47,XX,+mar[45]/
46,XX[10]
min(19)(:p12q13.1:)  M-FISH;
cenM;
MCB
see below {1} case 28  
Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; pregnancy terminated
  19-U-
2
male/
prenatal
AF de novo 47,XY,+mar[38]/
46,XY[17]
r(19)(::p13.11
q13.11-12::)[16]/
r(19;19)(::p13.11

q13.11-12:
:p13.11
q13.11~
12::)[2]/
min(19)(:p13.11

q13.11-12:)[5]
cenM;
subcenM
see below {0} provided by Dr. Mazauric, Düsseldorf, Germany  
Amniocentesis due to advanced  maternal age; no ultrasound abnormalities in week 15; spontaneous abortion after amniocentesis
  19-U-
3
male/
prenatal
AF de novo? 47,XY,+mar[100%] r(19)(::p12q12::) midi n.a. {9} case 4  
  19-U-
4
male/
prenatal
AF de novo 47,XY,+r[17%]/
46,XY[83%]
r(19) centromeric probes and wcp pregnancy terminated; autopsy result normal {10} case 5  
  19-U-
5
female/
prenatal
AF de novo 47,XX,+mar[10%]/
46,XX[90%]
min(19)(:p13.11q12:) cenM; subcenM Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; pregnancy was terminated - no additional information available {0} provided by Dr. Klein, Butzbach, Germany  
  19-U-
6
male/
prenatal
AF de novo 47,XY,dup(21)(q22.2q21.1),+r[18]/
46,XY,dup(21)(q22.2q21.1)[32]
r(19)(::p13.11q13.2::)*
sSMC derived from a maternal chromosome 19
different FISH probes, micro satellite analysis; UPD-test see below {8} case 3
{42}
 
Amniocentesis due to advanced  maternal age; Baby born by cesarean section at 40th week without complications, with hypotonia, dysmorphic craniofacial features including microcephaly, hypertelorism, upward slanting palpebral fissures, deep palmar and plantar crease; delayed myelinisation, psychomotor development moderately delayed at 9m. No Down syndrome features, which is in concordance with the lack of the DSCR.
  19-U-
7
female/
prenatal
AF
(EKF-
cellbank)
de novo 47,XX,+mar[10]/
46,XX[30]
min(19)(:p13.11q12:) 
FISH-data:
26.7-at least to 33.3MB
cenM; subcenM; UPD-test see below {23} case 13  
possible hypotrophy in US, parents 31y and non-consanguineous. Already one healthy 4 y old girl. Amniocentesis due to abnormal maternal screening (1/100); pregnancy terminated, no autopsy but fetus without abnormalities
  19-U-
8
n.a./
prenatal
AF de novo 47,+mar[100%] r(19) M-FISH; wcp 19 abnormal in 1st ultrasound. hydramnios {21} case 4  
  19-U-
9
n.a./
prenatal
AF de novo 47,+mar[100%] r(19) M-FISH; wcp 19 maternal serum screen test; TOP {21} case 12  
  19-U-
10
male/
prenatal
chord blood de novo 47,XY,+mar[28]/
46,XY[4]
r(19)(::p13.1q13.1::)[17]/
r(19;19)(::p13.1
q13.1:
:p13.1
q13.1::)[4]
FISH-data: breaks between 10.61-22.66 and 48.31-57.56 MB
 
M-FISH; subcenM, PCL-FISH
 
enhanced nuchal translucency, TOP {50} case 20  
  19-U-
11
female/
prenatal
AF de novo 47,XY,+mar[34%]/
46,XY[66%]
r(19)(::p11.1q12::) M-FISH; subcenM; UPD-test advanced maternal age, patient lost during follow up {0} provided by Drs. Wagner and Stibbe, Hannover, Germany  
  19-U-
12
female/
prenatal
AF de novo 47,XY,+mar[40%]/
46,XY[60%]
min(19)(:p11.1q13.1~
13.2:)[16]/
r(19)(::p11.1
q13.1~
13.2::)[8]/
r(19;19)(::p11.1
q13.1~13.2:
:p11.1
q13.1~13.2::)[1]
cenM-FISH; subcenM advanced maternal age, patient lost during follow up {0} provided by Drs. Wagner and Stibbe, Hannover, Germany  
  19-U-
13
n.a./
prenatal
AF n.a. 47,+mar[17%]/
46[83%]
r(19) wcp19; cep19 Advanced maternal age. no further information available TOP {37} case 13  
  19-U-
14
n.a./
prenatal
AF n.a. 47,+mar[60%]/
46[40%]
min(19)(:p12q13.1:)
aCGH: 24.08-40.50
wcp19; cep19, subcenM;
aCGH
n.a. {52} case Sm-9  
  19-U-
15
female/
postnatal
PBL n.a. 47,XX,+mar[?%] der(19)t(18;19) array-CGH psychomotor disorder {39} 1 case
{54}
 
  19-U-
16
male/
prenatal
AF n.a. 47,XY,+mar[100%] min(19)(:p13.11q11:) cenM, subcenM n.a. {0} provided by Dr. Alves, Porto, Portugal  
  19-U-
17
n.a./
prenatal
AF n.a. 47,+mar[100%] min(19)(:p12q12:)
aCGH: 33.10-33.59
cenM; subcenM;
array-CGH
amniocentesis due to advanced maternal age; no US abnormalities. No further info available {0} provided by Dr. Eiben, Oberhausen, Germany  
  19-U-
18
female/
prenatal
AF n.a. 47,+mar[?100%] mar(19) SKY n.a. {48} case F0534481  
  19-U-
18
male/
prenatal
AF de novo 47,XY,+mar[56]/
46,XY[47]
mar(19)(p1?2q13.11)
aCGH: 32.54-37.60
aCGH normal sonography, TOP {49}  
  19-U-
19
male/
newborn
PBL de novo 47,XY,+mar[20] min(19)(qterq13.43:
:p13.12
q13.2::q13.42qter)
or min(19)(qter
q13.42:
:p13.12
q13.2::q13.43qter)
aCGH, FISH (subtel 19qter, wcp 19) see below {0} provided by L. Fairbrother, Florida, USA    
facial abnormalities (incl. short philturm, palpebral fissures, simple proruding ears, blunted nose, microcephaly), cataracts, short stature, hypoplasti nipples and nails, single right kidney, undescended testes, imporferate anus, quattate psoriasis, VSD and PDA (self resolved), mental retardation, developmental delay, walk at 7 y without assistance and some receptove language
                     

 

 

 


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  
  19-N-
pt13.2/
1-1
n.a./
11m
PBL n.a. 47,+mar[30%]/
46[70%]
acc. to FISH
?inv dup(19)(pterq13.2: :q13.2pter) aCGH; RP11-19I2 developmental delay, short stature {47} case 8  
                     

 

 

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  
  19-N-
IMB-
pter/
1-1 to
1-2
see {30; 31} {30; 31}  
  19-N-
IMB-
qter/
1-1 to
1-13
see {32-36} {32-36}