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CHROMOSOME 16 |
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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 |
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the probably non-dosage sensitive pericentric region of chromosome 16
SCHEMATIC CYTOGENETIC DEPICTION
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} --- 28.73 uncritical region [34.40 centromere 45.50] uncritical region 46.02 --- 46.16 critical region
Below adapted for UCSC hg19, 2009
critical region ? {55} --- 28.83 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 |
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 |
see 16-Uu-1 | |||||||||
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. |
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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 |
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*** 16-O- p11.2/ 4-2 *** |
male/ |
AF | mat | 47,XY,+mar[60%]/ 46,XY[40%] |
mar(16)(:p11.2→q12.1:) aCGH(hg19): 28,825,250–46,356,412 |
aCGH | AMA?; mother normal | {71} case P7 | ||
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+,cos11+, cos13+,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 |
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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 |
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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 |
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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 |
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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 |
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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 |
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*** 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 |
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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 |
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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} |
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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. |
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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 |
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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 |
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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 |
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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 |
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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 |
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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} | ||
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 |
see +21-U-37 | |||||||||
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 |
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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 |
see 16-U-29 | |||||||||
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 |
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16-W- p10/ 1-1 |
see McCl-16-W-p10/1-1 | |||||||||
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 | ||
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 | |||||||||
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)(:p11.1→q12.1:) | 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 |
see 16-Uu-2 | |||||||||
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 | n.a. | 47,XX,+mar[33]/ 46,XX[30] |
r(16)(::p12.2→p11.2::) | midi | n.a. | {0} provided by Dr. Junge, Dresden | ||
16- U-40 |
male/ prenatal |
AF PBL |
de novo | AF:47,XY,+mar[10]/ 46,XY[31] PBL no sSMC at 1.5 years |
mar(16)(p11.1q22.1) aCHG (hg19): 46,492,626-68,867,969 |
aCGH UPD test |
born at 25 wog with 585g. At 1½ y short stature, congenital hypothyroidism, hearing impairment hypospadias |
{70} | ||
Cases with complex sSMC (Uc)
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- Uc-1 |
||||||||||
Cases with discontinous sSMC (Ud)
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- Ud-1 |
||||||||||
Cases with UPD (Uu)
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- Uu-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- Uu-2 |
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} | ||
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 |
see PsMcCl-16-N-p11.2/1-1 | |||||||||
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} | |||||||