tl_files/tiny_templates/Bilder TL/Header-sSMC.jpg

- sSMC -

CHROMOSOME 16

References

 

 

             
  Cases without
clinical findings		 37 Cases with
clinical findings		 16 symptoms  
  similar imbalances - no clinical findings similar imbalances with clinical findings  
  Cases with
unclear clinical correlation		 Cases with
neocentromeres		 3 tumor
0		  
  similar imbalances  
      DISCLAIMER      

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 16
mat		 UPD 16
pat		 UPD 16
unclear		  
           

 

the probably non-dosage sensitive pericentric region of chromosome 16

SCHEMATIC CYTOGENETIC DEPICTION

tl_files/tiny_templates/Bilder TL/sSMC/sSMC-16.jpg


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 ? {55} --- 28.86 uncritical region [34.40 centromere 45.50] uncritical region 46.02 --- 46.16 critical region

Below adapted for UCSC hg19, 2009

critical region ? {55} --- 28.96 uncritical region [34.60 centromere 47.00] uncritical region 47.50 --- 47.64 critical region

 

Clinical symptoms of centromere-near proximal imbalances

 

chromosomal region

 16p - proximal 16q - proximal
symptoms
developmental delay (100 %) (33 %)
dysmorphic face (0 %) (67 %)
growth retardation (0 %) (33 %)
genital abnormalities (0 %) (67 %)
hypotonia (0 %) (33 %)
mental retardation (100 %) (33 %)
number of cases (marked with “°” below) 1 3
 

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  
 
16-O-
p11.2/
1-1		 male/
prenatal		 AF n.a. 47,inv(X)(p11.4p22.3)Y,+mar[18]/
46,inv(X)(p11.4p22.3)Y[7]

min(16)(:p11.2→q11.1:) maternal UPD 16

 cenM; subcenM; UPD-test see below {26; 63}  
Amniocentesis due to advanced maternal age; spontaneous birth in week 39 of gestation; Apgar ?/10(10, weight 2960g; apart from posterior plagiocephaly no indication for malformations
16-O-
p11.2/
1-2		 female/
adult		 PBL
(EKF-
cellbank)		 n.a. 47,XX,+mar[33%]/
46,XX[67%]		 min(16)(:p11.2→q11.1:) cenM; subcenM normal woman, infertile {0} provided by Reprogenet, Spain
  ***
16-O-
p11.2/
2-1
***		 female/
prenatal		 AF, skin; PBL, placenta de novo AF: 47,XX,+r[8]/
46,XX[9]
skin, 50% of sSMC; PBL: 3-5% of sSMC
in placenta 47,XX,+16!		 r(16)(:p11.2→q12.2:)

FISH-data: RP11-360L15 (28.86 MB) on sSMC

 cenM,
subcenM; UPD-test		 see below {0} provided by Genzyme, USA  
sSMC detected due to advanced maternal age; Slowing of growth in the last weeks of pregnancy and labor was induced at 37.5 weeks. Weight was 2.55 kg; length 46.5 cm; scars at two sites on her left thigh from the fetal skin biopsy; deep sacral dimple, ultrasound of underlying structures was normal. Neonatal course also was normal. At 7 months of age she sits with assistance and is close to sitting alone. The remainder of developmental assessment is also normal for age. Normal at age of 4.5 y.
 
16-O-
p11.2/
3-1		 female/
prenatal		 AF n.a. 47,XX,+mar[22]/
46,XX[10]
 mar(16)(:p11.2→q1?1.2:)

aCGH: 31.68-34.85 MB

 aCGH sSMC detected due to hygroma colli - normal child born {62} case 16  
  16-O-
p11.2/
3-2		 female/
prenatal		 AF mat 47,XX,+mar[50%]/
46,XX[50%]		 min(16)(:p11.2→q11.2:) cenM, subcenM mother normal {0} provided from Serbia
  
  16-O-
p11.2
~11.1/
1-1		 male/
prenatal		 AF;
PBL;
Chord Fibroblasts		 de novo 47,XY,+mar[~50%]/
46,XY[~50%]
(mar in 75% of PBL and 30% of studied fibroblasts; repeat in blood: 64%)		 dic r(16) ( wcp16+, cos 11+, cos 13+, c3296+, D16z2++,D16Z3+)
r(16)(::p11.2~11.1→q11.2:
:q11.2→16p11.1::)		 specific FISH probes: wcp16; and mentioned probes see below {5}
{19} case 4		  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; child born without clinical symptom and healthy at 10m and 2y of age.
  16-O-
p11.1/
1-1		 male/
prenatal		 AF de novo 47,XY,+mar[16]/
46,XY[13]		 min(16)(:p11.1→q11.2:) cenM;
subcenM; UPD-test		 see below {1} case 24  
Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; child born without clinical symptom
  16-O-
p11.1/
1-2		 male, twins/
prenatal		 AF de novo mosaic - e.g. in one twin: 48,XY,+2mar[9]/
47,XY,+mar[14]/
46,XY[14]		 min(16)(:p11.1→q11.2:) cenM; subcenM; UPD-test see below {0} provided by Dr. Heilbronner, Stuttgart, Germany  
microsatellites tested for UPD: D16S2616, D16S769, D16S2624, D16S0539, D16S2621
Amniocentesis due to advanced maternal age, twin pregnancy, both twins with marker. Both children normal at birth and at 4 months
  16-O-
p11.1/
1-3		 see 16-O-p11.1/4-4    
  16-O-
p11.1/
1-4		 female/
35y		 PBL n.a. 47,XX,+mar[7]/
46,XX[3]		 min(16)(:p11.1→q11.2:)
in aCGH no euchromatin deteceted
 cenM;
subcenM
aCGH		 normal female, prior to ICSI {68} case 16-1
 
  16-O-
p11.1/
1-5		 n.a./
prenatal		 AF n.a. 47,+mar[87]/
46[13]		 min(16)(:p11.1→q11.2:) cenM;
subcenM		 healthy child born {0}  
  16-O-
p11.1/
1-6		 female/
prenatal		 AF n.a. 47,XX,+mar[100%] min(16)(:p11.1→q1?1.2:)
in aCGH practically no euchromatin deteceted: 34.47-35,01 MB		 aCGH normal {62} case 15
  
  16-O-
p11.1/
1-7		 male/
4y		 PBL mat 47,XY,+mar[10]/
46,XY[5]		 min(16)(:p11.1→q11.2)
in aCGH practically no euchromatin deteceted: 34.2-47,3 MB [hg19]
 subcenM
aCGH		 speech delay; normal mother, {0} provided by Dr.Martin, Homburg, Germany
  
  16-O-
p11.1/
1-8		 female/
prenatal		 AF de novo 47,XX,+mar[75%]/
46,XX[25%]		 min(16)(:p11.1→q11.2) subcenM
aCGH		 adv. mat. age, normal child born {0}  
  16-O-
p11.1/
1-9		 female/
adult
 PBL n.a. 47,XX,+mar[20%]/
46,XX[80%]		 min(16)(:p11.1→q11.2) cenM; subcenM normal but repeated abortions {0}  
  16-O-
p11.1/
2-1		 female/
n.a.		 PBL n.a. 47,XX+mar[73%]/
46,XX[27%]		 r(16)(:p?11.1→q?12.1:)* radioactive ISH; satellite II probe for chr.169 see below {3} mother is mentioned for case 3  
Marker present as well in one healthy daughter and one mentally and physically retarded and son.
  16-O-
p11.1/
3-1		 male/
prenatal		 AF de novo 47,XY,+mar[20%]/
46,XY[80%]		 dic(16;16)(:p11.1→q11.2:
:q11.2→p11.1:)		 cenM; subcenM; UPD-test Marker detected prenatally; normal child was born {0} provided by Dr. Pao-Lin,
Taiwan		  
  ***
16-O-
p11.1/
4-1
***		 male/
prenatal		 AF de novo 47,XY,+mar[25]/
46,XY[28]		 min(16)(:p11.1→q12.1:)
FISH-data: RP11-474B12 (45.87-46.02) on sSMC		 M-FISH; subcenM; UPD-test see below {0} provided by Drs. Prager and Junge,
Dresden, Germany		  
microsatellites tested for UPD : 16S520; D16S3068; D16S423
Marker detected prenatally due to advanced maternal age; normal child was born birth weight 2970g; length 52cm; walking with 10.5months; minor aberrations: incomplete simian crease at one hand and sacral porus
  16-O-
p11.1/
4-2		 male/
adult		 PBL
(EKF-
cellbank)		 n.a. 47,XY,+r[?%] min(16)(:p11.1→q12.1:) cenM; subcenM Marker detected in normal male, cytogenetics due to abnormal baby with del(2) {27} case 9; {32}  
  16-O-
p11.1/
4-3		 male/
prenatal		 AF/ CH n.a. chorion: 47,XY,+mar[2]/46,XY[1], amnion: mar in 3/15 metaphases min(16)(:p11.1→q12.1:)
array-CGH - euchromatic size 366.3 kb in 16q; RP11-627O2 (45.38-45.60MB), RP11-825K2 (45.36-45.90MB), RP11-719K16 (45.47-45.89MB)
 cenM; subcenM; array CGH advanced maternal age; normal child at 7 months {0} provided by abCorp Dynacare Laboratories, USA  
  ***
16-O-
p11.1/
4-4
***		 male/
prenatal		 AF de novo 47,XY,+mar[100%] min(16)(:p11.21→q12.1:)
 FISH-data: RP11-474B12 (45.87-46.02) on sSMC
array: 31.43-45.76 MB		 centromeric probes; subcenM; array-CGH; UPD-test see below {0}
{43}		  
microsatellites tested for UPD: D16S2616, D16S748, D16S403, D16S769, D16S402
Amniocentesis due to advanced maternal age. At birth weight 4,055 gr. length 54 cm and OFC 37.5 cm. At 1 y phenotypically and neurologically normal.
  16-O-
p11.1/
4-5		 n.a./
prenatal		 AF maternal
(mother 50%)		 47,XN,+mar[20%]/
46,XN[80%]		 min(16)(:p11.1→q12.1:)
in aCGH no euchromatin deteceted		 cenM, subcenM twin pregnancy; mother normal; sSMC only in one twin {0} provided by Dr. Nurit Israel  
  16-O-
p11.1/
4-6		 female/
adult		 PBL n.a. 47,XX,+mar[30-40%]/
46,XX[60-70%]		 min(16)(:p11.1→q12.1:) cenM; subcenM; UPD-test advanced maternal age, normal baby born {0} provided by Dr. Magdalini Lagou, Greece  
  16-O-
p11.1/
4-7		 male/
44y		 PBL n.a. 47,XY,+mar[9]/
46,XY[21]		 r(16)(::p11.1→q12.1::) cenM; subcenM normal male, infertulity {68} case 16-2  
  16-O-
p11.1/
5-1		 female/
37y		 PBL
cell line at ECACC DD0375		 de novo 47,XX,+mar[28]/
46,XX[22]		 min(16)(:p11.1→q11.1:) all available centromeric probes; cenM, subcenM, midi; UPD-test see below {2} case 17
{9} case 23
{25} case 7		  
clinically normal; son with same marker; mar discovered in amniocentesis due to advanced maternal age; baby normal at 4m
  16-O-
p11.1/
5-2		 female/
adult		 PBL n.a. 47,XX,+mar[80%]/
46,XX[20%]		 min(16)(:p11.1→q11.1:) cenM; subcenM see below {0} provided by Dr. Hansmann, Halle, Germany  
clinically normal; daughter with same marker; mar in same percentage; discovered in amniocentesis due to advanced maternal age; no info available on daughter
  16-O-
p11.1/
5-3		 female/
prenatal		 AF paternal (mar in 4-10% of PBL) 47,XX,+mar[90-97%]/ 46,XX[10-3%] min(16)(:p11.1→q11.1:)* M-FISH; all cep, 16q11.2 probe; CGH amniocentesis due to advanced maternal age; father normal {50} case 2  
  16-O-
p11.1/
5-4		 female/
31y		 PBL
(EKF-
cellbank)		 n.a. 47,XX,+mar[100%] min(16)(:p11.1→q11.1:) cenM; subcenM no abnormal phenotype; 6 years infertility, 3 x inseminations failed {0} provided by Reprogenet, Spain  
  16-O-
p11.1/
6-1		 male/
prenatal		 AF de novo 47,XY,+mar[?%]/
46,XY[?%]		 r(16)(:p11.1→q11.1:) subcenM; UPD-test see below {0} provided by Dr. Virginia Palente, USA  
amniocentesis due to advanced maternal age; healthy child born
  16-O-
p11.1/
6-2		 female/
prenatal		 AF de novo 47,XX,+mar[100%] r(16)(:p11.1→q11.1:) pericentric BAC probe set amniocentesis due to ?; child normal {65} case 14  
  16-O-
p11.1/
7-1		 male/
adult		 PBL
(EKF-
cellbank)		 n.a. 47,XY,+mar[8]/
46,XY[42]		 min(16)(:p11.1→q11.1~11.2:) cenM; subcenM normal male, infertile {0} provided by Reprogenet, Spain  
  ***
16-O-
p10/
1-1
***		 female/
25y		 PBL n.a. 47,XX,+mar[15]/
46,XX[3]		 min(16)(:p10→q12.1:)[80%]/
min(16)(q12.1→p10:
:p10→q12.1:)[20%]
FISH-data: RP11-474B12 (45.87-46.02) on sSMC		 cenM; subcenM normal but daughter with sSMC and Rett syndrome (mol. confirmed) {0} provided by Drs. Prager and Junge,
Dresden, Germany		  
                     

 

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  
  16-O-
IMB-
p11.2/
1-1 +
review		 female and male/
adult		 PBL familial 46,dup(16)(p11.2q11) locus specific probes normal adults {19} - other papers reviewed  
  16-O-
IMB-
q12.1/
1-1		 female and male/
adult		 PBL familial 46,dup(16)(q11.2q12.1) locus specific probes normal adults {38} family 2  
                   


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  
  16-
CO-
1		 female/
prenatal		 AF
PBL		 de novo 47,XX+mar[20%]/
46,XX[80%]
(postnatal mar in 16% of PBL)		 dic(16) .ish(D16Z2++,wcp16+) cep for 1, 6, 9, 1/5/19, 13/21, 14/22, 15, 16; wcp 16 see below {6}  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; child born without clinical symptom and healthy at 9m of age.
  16-
CO-
2		 male/
prenatal		 AF maternal
(no info on mosaic status)		 47,XY,+mar[21]/
46,XY[14]		 mar(16).ish(D16Z1+) FISH with all available centromeric probes Amniocentesis due to abnormal serum biochemistry; normal at 14m; mother clinically normal {8} case 16  
  16-
CO-
3		 female/
24y		 PBL/ Fibroblasts paternal 47,XX,+mar[1761]/
46,XX[239]
(in 915/1000 fibroblasts)		 min(16) .ish(D16Z1+) FISH with all available centromeric probes normal phenotype - mar present in sister as well {11} case 1  
  16-
CO-
4		 male/
42y		 PBL de novo? 47,XY,+mar[60]/
46,XY[40]		 r(16) SKY; cep 16 repeated abortions (?) {16} case 11
{42} case 93
{68} case 16-3
  
  16-
CO-
5		 female/
18m		 PBL de novo 47,XX,+mar[?100%] mar. ish der(16)(wcp16+,cos97+,cos33+,
cos11+,D16Z2+,D16Z3-), cosmids in 16p11.2		 wcp16, cos97, cos33, cos11, D16Z2, D16Z3 see below {0} case provided by UNIQUE  
normal phenotype, apart from being an extra digit on left hand, extra digit attached to left hand by a piece of skin with no bone but a small nail
  16-
CO-
6		 n.a./
prenatal		 AF de novo 47,+mar[43%]/
46,XY[57]		 mar(16)
(wcp+, cep+)		 wcp; cep 16 normal child born and normal at 11 months {52}
{67} case 17
  
  16-
CO-
7		 female/
33y		 PBL n.a. 47,XX,+r[100%] r(16) SKY normal woman, repeated abortions {61} case F047204
{68} case 16-4
  
  16-
CO-
8		 male/
prenatal		 AF de novo 47,XY,+mar[100%] mar(16)
(cep+, wcp-)
in aCGH no euchromatin		 wcp, cep, aCGH normal child born {0}  
                     

 

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  
  16-W-
p11.2/
1-1		 moved to +21-U-37
 {0} provided by Dr. S.W. Cheung, Houston, USA  
  16-W-
p11.2/
2-1 °
 male/
6y		 PBL n.a. 47,XY,+mar[14]/
46,XY[15]		 min(16)(:p11.2→q11.2:) cenM, subcenM slight cognitive deficit {0} provided by Dr. C. Alves, Porto, Potugal  
  ***
16-W-
p11.2/
3-1
***		 female/
prenatal		 chord blood de novo 47,XX,+mar[25%]/
 46,XX[75%]		 r(16)(::p11.2→q12.1::)
 array: 31.65-46.16 MB		 cenM, subcenM, midi; array-CGH see below {51} case 7  
Amniocentesis due to advance maternal age with no ultrasound anomalies. TOP. Autopsy at 23 weeks of gestation revealed a female fetus with an extra supra-renal near the left ovary and slight facial alterations, like discrete hypertelorism, large philtrum and asymmetrical implantation of the ears.
  16-W-
p11.2/
3-2		 male/
prenatal		 AF de novo 47,XY,+mar[100%] r(16)(::p11.2→q12.1::) cenM, subcenM; UPD-test see below {0} provided by Dr. Borochowitz, Israel  
Amniocentesis due to advance maternal age; sonography and fetal brain MRI (normal). At age of 31 w severe IUGR was noted, and the couple chose to have a TOP. Placental culture revealed 2 lines: 7 cells with mar, 6 cells with trisomy 16.
  16-W-
p11.2/
3-3		 male/
3y		 PBL
(EKF-
cellbank)		 de novo 47,XY,+mar[5]/ 46,XY[27%] r(16)(::p11.2→q12.1::)
aCGH: 9,875,000-35,005,000 MB
 cenM, subcenM; UPD-test
aCGH		 see below {0} provided by Dr. Martin, Homburg, Germany  
Ataxia when standing and walking, delay in speech development, developmental regression ~3 y
  16-W-
p11.1/
1-1 °
 male/
2y		 PBL de novo 47,XY,+mar[6%]/
46,XY[94%]		 min(16)(:p11.1→q11.1 or q11.1→p11.1:
:p11.1→q11.2:)
array: 32.56-45.44
FISH probe in p at 26.7MB		 midi, subcenM; aCGH see below {22} case 16-1  
normal at birth, progredient edema at hands at 9m; little asymmetry of skull, no dysmorphic signs, slight penis anomaly
  16-W-
p11.1/
2-1 °		 male/
13y		 PBL de novo 47,XY,+r[7]/
46,XY[7]		 r(16)(::p11.1→q12::) midi, cenM, subcenM see below {44} case 23
{51} case 8		  
congenital malformations, born at term, birth weight 3200g, length 50cm; at 13 y: weight 47 kg, length 160,5cm, OFC=54cm, low-set dysplastic ears, hypoplastic testes OD, cryptorchidism
  16-W-
p11.1/
3-1		 moved to 16-U-29 {63}  
  16-W-
p11.1/
4-1 °		 male/
4y		 PBL de novo 47,XY,+mar[16]/ 46,XY[4] mar(16)(:p11.1→q12.2::)
 array: 45.50-48.57 MB
 array-CGH see below {58; 60}  
IUGR at 31w gestation, delivery induced at 36 weeks, birth weight 1,730 g. poor sucking and general psychomotor delay. At age of 4y microcephally, high nasal bridge, deep set eyes, thin lips, mild retrognatia, low muscle tone, wide-based gait due to clumsiness or ataxia, used only 5 verbal words, MRI revealed cerebellar cortical dysplasia, large forth ventricle with mild elongated superior cerebellar peduncles and small vermis with atrophy of the inferior aspect were noted.
  16-W-
p11.1/
5-1		 female/
6y		 PBL n.a. 47,XX,+mar[73%]/
46,XX[27%]		 min(16)(:p11.1→q11.2:) cenM, subcenM mental retardation
 {0} provided by Dr. Noa Ephron, Israel
  
  16-W-
p10/
1-1		 see McCl-16-W-p10/1-1
 {13}  
                     

 

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  
  16-W-
IMB-
p12/
1-1		 male/
2y		 PBL de novo 46,XY,dup(16)(pter→p11.2:
:p12→qter)		 n.a. see below {36}  
at 16 months tremor-like movements and occular revulsions lasting several seconds without loss of consciousness; microphtalmia, strabismus, hypertelorism. epicanthus, cleft palate, short neck, atopic body eczema, truncal hypotonia, moderate motor retardation, psychomotor delay, developmental delay, autism(?); epilepsy (?)
  16-W-
IMB-
p12.2/
1-1		 male/
25y		 PBL n.a. 46,XY,dup(16)(pter→p11.2:
:p12.2→qter)		 locus specific FISH-probes {34} see below {34}case 1  
psychomotor delay since birth, episodes of seizures; at age of 3 years diagnosed as autistic, severely mentally retarded and epilepsy; at 25 y: weight and height >3rd centile, OFC 25th centile.
  16-W-
IMB-
p12.2/
1-2		 female/
5y		 PBL mat 46,XX,dup(16)(pter→p11.2:
:p12.2→qter)		 locus specific FISH-probes {34} see below {34}case 2; {35}  
borderline cognitive impairment (IQ 80), behavioral problems; autism (?); mother similarly impaired in intelligence
  16-W-
IMB-
p12.1/
1-1		 male/
prenatal		 AF de novo 46,XY,dup(16)(pter→p11.2:
:p12.1→qter)		 wcp 16; locus specific FISH-probes {33} see below {33}  
prenatal diagnosis due to advanced maternal age; no sonographic abnormalities; mother described tremor like child movements; parents decided for TOP at week 24 of gestation; no autopsy was performed.
  16-W-
IMB-
p12.1/
1-2		 male/
postnatal		 PBL maternal 46,XY,dup(16)(pter→p11.2:
:p12.1→qter)		 n.a. see below {47}  
developmental delay and learning difficulties in mother and patient
  16-W-
IMB-
q11.2/
1-1		 male/
28y		 PBL de novo 46,XY,dup(16)(pter→q13:
:q11.2→qter)		 locus specific FISH-probes {28} see below {28}  
severe growth and mental retardation; short stature, <3rd centile, self-destructive behavior, quadripleagia with bilateral pes cavus; he was hypotonic during first years of live and showed developmental delay, no speech
  16-W-
IMB-
q11.2/
2-1		 male/
newborn		 PBL de novo 46,XY,inv dup ins(16) (pter→q11.2::q12.2→q11.2:
:q11.2→q12.2::q11.2→q11.2:
:q12.2→qter)		 specific FISH-probes {38} see below {38}case 1  
Born at term; birth weight 3.35 kg, length 51 cm and OFC of 34 cm; ascertained at 13 days of age with aortic isthmus stenosis. At 15 months, stature 81 cm within the normal range but both weight of 10 kg and OFC of 44.5 cm below the 25th centile. Motor developmental delay; unilateral inguinal hernia later operated on. At the age of 5: motor development retardation, mental and speech delay and his behavior was autistic; round face, strabismus, hypermetropia, normal fundus oculi, a long flat philtrum and normal dentition. stature again within the normal range but microcephaly, a mildly short neck, obesity and a hydrocele, mildly tapering fingers and mild plano-valgus positioning of his feet.
  16-W-
IMB-
q11.2/
3-1		 male and female/
adult		 PBL familial 46,inv dup ins(16)(q11.2q13q11.2) specific FISH-probes {38} see below {38} family 1  
different abnormalities as reported in {38}
  16-W-
IMB-
q11.2/
3-2
to 3-4		 similar as case above {39-42}  
  16-W-
IMB-
q11.2/
4-1
to 4-7		 array-CGH study; 7 cases with microduplication in 16q11.2; 3/7 maternally inherited, 1/7 paternally inherited.
in 3 cases autism, ADHD and language delay		 {39-42}  
  16-W-
IMB-
q11.1/
1-1		 female/
22y		 PBL n.a. 46,dup(16)(q11.1q12.2)
aCGH: 45.03-56.51 MB		 array-CGH see below {59}  
different abnormalities as reported in {59}
                   


W-cases with unclear/insufficient characterization of the sSMC (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  
  16-
CW-
1		 male/
30y		 PBL
cell line at ECACC DD1135		 de novo 47,XY,+mar[100%] mar(16).ish(DZ16Z2+; D16Z3+, wcp16-) FISH with all available centromeric probes; wcp16, UPD-test mild mental handicap; psychosis; schizophrenia, normal appearance without abnormalities {2} case 15
{9} case 21		  
  16-
CW-
2		 female/
prenatal		 AF de novo 47,XX,+mar[12]
(interphase in uncultured amniocytes: mar in 88%)		 mar(16) FISH with all centromeric probes; wcp16 see below {20}  
amniocentesis due to posterior fossa cyst with extension of the region of cerebellar vermis with splaying of cerebellar hemispheres suggesting Dandy-Walker complex in week 20 of gestation; termination of pregnancy in week 23; no autopsy, external examination showed normal female phenotype.
  16-
CW-
3		 male/
postnatal		 PBL de novo 47,XY,+mar[50%]/
46,XY[50%]		 mar(16).ish(DZ16Z2+; D16Z3+, wcp16-) M-FISH see below {29}  
patient born at term after normal pregnancy and delivery: 3150g, 51cm, OFC 35.5cm. facial dysmorphic; epicanthic folds, thin, distinct eyebrows, simian crease in both hands, short neck, perimembarnotic VSD and open foramen ovale, delayed development; up to 3y of age patient progressed at -2SD, weight +5% and OFC at -2.5 SD curve.
  16-
CW-
4		 female/
2y		 PBL n.a. 47,XX,+mar[31]/
46,XX[21]		 mar(16)(:p1?1→q12:)
mlpa p181x3		 MLPA; cep 16 mental retardation {0} provided by Dr. A. Delicado Navarro, Spain  
  16-
CW-
5		 female/
2y		 PBL n.a. 47,XX,+r[100%] r(16) SKY seizures {61} case F0616779  
                     

 

 

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  
  16-
U-1		 see mult 2-11 {7}  
  16-
U-2		 female/
prenatal		 AF de novo 47,XX,+mar[36]/
46,XX[19]		 mar(16) .ish(D16Z1+) all centromeric probes see below {8} case 9  
Amniocentesis due to abnormal serum biochemistry; pregnancy terminated; no obvious abnormalities in post-mortem examination
  16-
U-3		 female/
prenatal		 AF de novo 47,XX,+mar[40]/
46,XX[10]		 mar(16) .ish(D16Z2dim; D16Z3+, wcp16-) all centromeric probes; wcp16 see below {9} case 20  
Amniocentesis due to advanced  maternal age;  pregnancy terminated
  16-
U-4		 male/
prenatal		 AF maternal
(mar in 15%)		 47,XY+mar[50%]/
46,XY[50%]		 r(16) FISH with all available centromeric probes n.a., as pregnancy terminated {4} case 8  
  16-
U-5		 female/
prenatal		 AF
fetal fibroblasts
and blood		 de novo 47,XX,+mar[2]/
46,XX[13]
sSMC not present in fetal blood; 21% of fetal fibroblasts with sSMC		 mar(16) .ish(wcp16+) all wcp probes see below {12}  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated; postmortem analysis revealed normal fetal phenotype
  16-
U-6		 see 16-U-15    
  16-
U-7		 male/
prenatal		 AF de novo 47,XY,+mar[60]/
46,XY[34]		 r(16)(::p1?1→q1?1.2::) wcp 16 probes
centromeric probes		 see below {21} case 11  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated; postmortem analysis revealed normal fetal phenotype
  16-
U-8		 female/
prenatal		 AF de novo 47,XX,+mar[21]/
46,XX[17]		 r(16;16)(::p1?1→q1?1.2:
:p1?1→q1?12::)		 wcp 16 probes
centromeric probes		 see below {21} case 31  
Amniocentesis due to advanced maternal age and anxiety; no ultrasound abnormalities; pregnancy terminated; postmortem analysis not available
  16-
U-9		 male/
prenatal		 AF de novo 47,XY,+mar[9]/
46,XY[2]		 r(16;16)(::p11.1→q12.1:
:p11.1→q12.1::)
 aCGH: 30.20-45.74 MB		 cenM; midi, array-CGH; UPD-test see below {0} provided by Dr. Mitulla, Suhl, Germany  
Amniocentesis due to advanced maternal age; no ultrasound abnormalities; termination of pregnancy; autopsy: no dysmorphism.
  16-
U-10		 male/
prenatal		 AF de novo 47,XY,+mar[6]/
46,XY[6]		 mar(16)(p13.1q12.2)* midi see below {23}  
Amniocentesis due to advanced maternal age and increased fetal nuchal translucency thickness in ultrasound in week 17 of pregnancy; termination of pregnancy; autopsy showed a male fetus with small, flat nose and broad nose bridge. Eyes, ears, mouth and palate were normal. The neck was broad. All body measurements were within normal limits for gestational age (weight:544 g; length: 20 cm; head circumference: 21 cm; femur length: 4.0 cm; foot length: 4.2 cm).
  16-
U-11		 n.a./
prenatal		 AF de novo 47,+mar[13]/
46[47]		 r(16) cep probes, wcp 16 see below {24} case 16  
Amniocentesis due to advanced maternal age and abnormal triple test. TOP, no postmortem abnormalities detected.
  16-
U-12		 male/
prenatal		 AF] de novo 47,XY,+mar[100%] min(16)(:p11→q11.2:) cenM, subcenM Amniocentesis due to advanced maternal age. Patient lost during follow-up {44} case 25  
  16-
U-13		 female/
prenatal		 AF n.a. 47,XX,+mar[47]/
46,XX[5]		 min(16)(:p11.1~11.2→q11.1:) cenM, subcenM; UPD-test Amniocentesis due to advanced maternal age. Patient lost during follow-up {0} provided by Drs. Epplen and Klein, Bochum, Germany  
  16-
U-14		 male/
prenatal		 AF n.a. 47,XY,+mar[?%]/
46,XY[?%]		 min(16)(:p11.1→q11.1:) cenM, subcenM Amniocentesis due to advanced  maternal age. Patient lost during follow-up {0} provided by Dr. Arndt, Hamburg Germany  
  16-
U-15		 n.a./
postnatal		 PBL de novo 47,+mar[85%]/
46,XX[15%]		 mar(16)(:p11.2→q11.2:)*
size p 0.7MB		 n.a.; subcenM with 3 BACs; array CGH see below {18}, {30} case 16  
macroglossia, dysmorphic features, height, weight and OFC ~90 centile; mild gross motor delay, asymmetric lower extremities; clinical features suggestive of Beckwith-Wiedemann syndrome - testing for LIT1 methylation confirmed a diagnosis of BWS.
  16-
U-16
to 18		 n.a./
n.a.		 n.a. n.a. 47,+mar[?%] mar(16) wcp probes no info available {45} 3 cases  
  16-
U-19		 male/
prenatal		 CH n.a. 47,XY,+mar[100%] min(16)(:p11.1→q11.2:) cenM, subcenM enhanced nuchal translucency in early pregnancy; TOP {54} case 22  
  16-
U-20		 male/
prenatal		 AF
chord blood		 de novo CB:
48,XY,+mar1,
+mar2[67%]/
47,XY,+mar1[22%]/
46,XY[11%]
AF: 2mar: 6-42%, 1mar: 28-48%		 mar1: dic(16)
mar2: min(16)		 M-FISH; all cep, 16q11.2 probe; CGH reason for amniocentesis neural tube defect; no follow up data available {50} case 3  
  16-
U-21		 female/
prenatal		 AF de novo 47,XX,+mar[12]/
46,XX[4]		 min(16)(:p11.1→q11.1:) cenM, subcenM advanced maternal age, TOP {0} provided by Genzyme, USA  
  16-
U-22		 male/
prenatal		 AF de novo 47,XY,+mar[18]/
46,XY[7]		 min(16)(:p11.1→q11.2:) cenM, subcenM advanced maternal age; patient lost during follow up {0} provided by Dr. Junge, Dresden, Germany  
  16-
U-23		 female/
prenatal		 AF n.a. 47,XX,+mar[6]/
46,XX[14]		 min(16)(:p11.1→q11.1:) cep probes, MLPA advanced maternal age {56} case 18  
  16-
U-24		 n.a./
prenatal		 AF de novo 47,+mar[26%]/
46[74%]		 mar(16)(:p11.2→q11.2:)
including microdel/-dup critical region		 cep probes, array-CGH; subcenM advanced maternal age; no sonographic signs {57}  
  16-
U-25		 female/
prenatal		 AF n.a. 47,XX,+mar[7]/
46,XX[12]		 mar(16) cep probes, array-CGH; subcenM n.a. {61} case F0548089  
  16-
U-26		 female/
prenatal		 AF n.a. 47,XX,+mar[100%] mar(16) SKY advanced maternal age {61} case F0751841  
  16-
U-27		 n.a./
prenatal		 AF n.a. 47,XN,+mar[?%]/
46,XN[?%]		 min(16)(:p11.1q12.1:) cenM, subcenM n.a. {0} provided by Dr. Fusun Duzcan, Turkey
  
  16-
U-28		 female/
prenatal		 fibroblasts n.a. 47,XX,+mar[14]/
46,XX[36]		 min(16)(:p11.1→q11.1:) cenM, subcenM spontanous abort after ICSI {0} provided by Dr. Mitter, Leipzig, Germany
  
  16-
U-29		 male/
prenatal		 AF n.a. 47,XY,+mar[27]/
46,XY[5]		 r(16)(::p11.1→q11.2::)
maternal UPD 16		 cenM, subcenM; UPD-test Dandy Walker Cyst and brain malformations; TOP {63}  
  16-
U-30		 female/
prenatal		 AF de novo 47,XX,+mar[?%]/
46,XX[?%]		 mar(16)(q11.2q12.1)
 45,279,306-45,618,257		 aCGH twin pregnancy - sonography normal {0} provided by Dr. Lemke, Bern, Switzerland
  
  16-
U-31		 male/
prenatal		 AF n.a. 47,XY,+mar[6]/
46,XY[11]		 r(16)(::p12.2→q11.2:) ceps, subcenM advanced maternal age, no sonographic signs, TOP {0} provided by Dr. Graf, Hildesheim, Germany  
  16-
U-32 to U-33
 n.a./
postnatal		 PBL n.a. 47,XN,+mar[?%] r(16) FISH n.a. {64} 2 cases  
  16-
U-34		 male/
prenatal
 AF de novo 47,XY,+mar[8]/
46,XY[22] 		min(16)(:p11.2→q11.2:) cenM, subcenM; UPD-test advanced maternal age, no info available
 {0} provided by Dr. Ebner, Regensburg, Germany
  
  16-
U-35		 female/
prenatal		 AF de novo 47,XX,+mar[100%] min(16)(:p12.1→q11.2:) cenM, subcenM TOP {0} provided by Dr. Gerard, Israel
  
  16-
U-36		 n.a./
prenatal		 AF de novo 47,XN,+mar[50%]/
46,XN[50%]		 r(16)
(::p11.2→q11.2::) 		cenM, subcenM increased nuchal transluciency, TOP
{0} provided from Portugal  
  16-
U-37		 male/
prenatal		 AF n.a. 47,XY,+mar[21]/
46,XY[11]		 min(16)(:p11.1→q12.1:) cenM, subcenM AMA; baby born, no further info {0} provided by Djordjevic, Serbia  
  16-
U-38		 female/
8y		 PBL n.a. 47,XX,+mar[5]/
46,XX[45]		 mar(16) M-FISH short stature, elevated TSH level {69} case 10  
  16-
U-39		 female/
prenatal		 AF   47,XX,+mar[33]/
46,XX[30]		 r(16)(::p12.2→p11.2::) midi n.a. {0} provided by Dr. Junge, Dresden  
                     

 

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  
  16-N-
mar/1		 n.a./
n.a.		 PBL? n.a. 47,+mar[?] mar(16) SKY possible velocardiofascial syndrome {14} case 7  
  16-N-
p11.2/
1-1		 male/
prenatal		 AF de novo 47,XY,i(16)(q10),+mar[15] min(16)(pter→p11.2:) SKY; region-specific PAC and BAC probes (acc. to {17}) see below {17; 31}  
in week 32 of gestation: IUGR, cardiac malformations (pulm. arterial hypoplasia with large septal defect), megacystis; TOP in week 35; autopsy revealed additionally antimongoloid palpebral fissures, maxillary hypoplasia, beaked nose, camptodactyly of both hands, hallux vagus of right foot, ambiguous external genitalia, megacystis with urethral stenosis, left pulmonary isomerism, veriam and olfactory bulb hypoplasia
16-N-
p11.2/
2-1		 male/
prenatal		 AF de novo 47,XY,+mar[11]/
46,XY[12]		 r(16)(p11.2p11.2)
aCGH: 29.09-29.51 MB		 aCGH AMA, TOP {66} case AF-13
                     

 

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  
  16-N-
IMB-
pter/
mult		 different p-arm duplications see {48} {48}  
  16-N-
IMB-
p13/
1-1		 n.a./
newborn		 PBL de novo 46,dup(16)(pterp13) wcp 16 see below {37}  
  multiple congenital anomalies including bilateral cleft of lip and palate, club-hands and feet, and heart defects  
  16-N-
IMB
q23/
1-1		 female/
newborn		 PBL de novo 46,XX,dup(16)(qterq23) wcp 16 see below {46}  
cardiopulmonary depression, severe hypotonia, bradycardia, APGAR 5/7; (40th week of gestation) birth weight 1840g, length 45cm, OFC 31 cm; hypertelorism, proptosis, prominent nose, dysmorphic, low set ears, thin upper lip, cleft palate, micrognathia, anteriorly placed anus. at 1 y, severe psychomotor retardation became evident (MRI: diffuse cerebral atrophy)
  16-N-
IMB-
qter/
mult		 different q-arm duplications see {48} {49}