CHROMOSOME 16

References

Cases without clinical findings	38	similar imbalances no clinical findings
Cases with clinical findings	16	similar imbalances with clinical findings	symptoms
Cases without clear clinical correlation	37	Cases with complex sSMC	0
Cases with discontinous sSMC	0	Cases with UPD and sSMC	2
Cases with neocentromeres	3	similar imbalances	DIS- CLAIMER
tumor	0	similar imbalances	DIS- CLAIMER

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

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	16p - proximal	16q - proximal
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	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
* 16-O- p11.2/ 2-1 *	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.							{0} provided by Genzyme, USA
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/ 4-1 *	male/ prenatal	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/ 5-1	male/ 44y	PBL	n.a.	47,XY,+mar[50%]/ 46,XY[50%]	r(16)(:p11.2→q12.1:)	cenM, subcenM	transsexuality	{0} provided by Dr. Hentze, Heidelberg, Germany
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
16-O- p11.2 ~11.1/ 1-1	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; child born without clinical symptom and healthy at 10m and 2y of age.							{5} {19} case 4
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
16-O- p11.1/ 1-1	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; child born without clinical symptom							{1} case 24
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
16-O- p11.1/ 1-2	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							{0} provided by Dr. Heilbronner, Stuttgart, Germany
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
16-O- p11.1/ 2-1	Marker present as well in one healthy daughter and one mentally and physically retarded and son.							{3} mother is mentioned for case 3
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
* 16-O- p11.1/ 4-1 *	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							{0} provided by Drs. Prager and Junge, Dresden, Germany
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}
* 16-O- p11.1/ 4-4 *	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.							{0} {43}
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
16-O- p11.1/ 5-1	clinically normal; son with same marker; mar discovered in amniocentesis due to advanced maternal age; baby normal at 4m							{2} case 17 {9} case 23 {25} case 7
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
16-O- p11.1/ 5-2	clinically normal; daughter with same marker; mar in same percentage; discovered in amniocentesis due to advanced maternal age; no info available on daughter							{0} provided by Dr. Hansmann, Halle, Germany
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
16-O- p11.1/ 6-1	amniocentesis due to advanced maternal age; healthy child born							{0} provided by Dr. Virginia Palente, USA
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}
16- CO- 1	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; child born without clinical symptom and healthy at 9m of age.							{6}
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
16- CO- 5	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							{0} case provided by UNIQUE
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	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
* 16-W- p11.2/ 3-1 *	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.							{51} case 7
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
16-W- p11.2/ 3-2	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.							{0} provided by Dr. Borochowitz, Israel
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: 29,875,000-35,005,000 MB	cenM, subcenM; UPD-test aCGH	see below	{0} provided by Dr. Martin, Homburg, Germany
16-W- p11.2/ 3-3	Ataxia when standing and walking, delay in speech development, developmental regression ~3 y							{0} provided by Dr. Martin, Homburg, Germany
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
16-W- p11.1/ 1-1 °	normal at birth, progredient edema at hands at 9m; little asymmetry of skull, no dysmorphic signs, slight penis anomaly							{22} case 16-1
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
16-W- p11.1/ 2-1 °	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							{44} case 23 {51} case 8
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}
16-W- p11.1/ 4-1 °	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.							{58; 60}
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

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}
16- CW- 2	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.							{20}
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}
16- CW- 3	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.							{29}
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
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
16- U-2	Amniocentesis due to abnormal serum biochemistry; pregnancy terminated; no obvious abnormalities in post-mortem examination							{8} case 9
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
16- U-3	Amniocentesis due to advanced maternal age; pregnancy terminated							{9} case 20
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}
16- U-5	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated; postmortem analysis revealed normal fetal phenotype							{12}
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
16- U-7	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated; postmortem analysis revealed normal fetal phenotype							{21} case 11
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
16- U-8	Amniocentesis due to advanced maternal age and anxiety; no ultrasound abnormalities; pregnancy terminated; postmortem analysis not available							{21} case 31
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
16- U-9	Amniocentesis due to advanced maternal age; no ultrasound abnormalities; termination of pregnancy; autopsy: no dysmorphism.							{0} provided by Dr. Mitulla, Suhl, Germany
16- U-10	male/ prenatal	AF	de novo	47,XY,+mar[6]/ 46,XY[6]	mar(16)(p13.1q12.2)*	midi	see below	{23}
16- U-10	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).							{23}
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
16- U-11	Amniocentesis due to advanced maternal age and abnormal triple test. TOP, no postmortem abnormalities detected.							{24} case 16
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
16- U-15	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.							{18}, {30} case 16
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}
16- Uu-1	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							{26; 63}
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}

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	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}
16-N- IMB- p13/ 1-1	multiple congenital anomalies including bilateral cleft of lip and palate, club-hands and feet, and heart defects						{37}
16-N- IMB q23/ 1-1	female/ newborn	PBL	de novo	46,XX,dup(16)(qterq23)	wcp 16	see below	{46}
16-N- IMB q23/ 1-1	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)						{46}
16-N- IMB- qter/ mult	different q-arm duplications see {48}						{49}