SMALL SUPERNUMERARY MARKER CHROMOSOMES - sSMC 19 -

           References

In general 70% of sSMC carriers are clinically normal. The figures here
are based on the bias, that mainly clinically aberrant cases are reported in literature!

UPD (uniparental disomy) cases:           UPD 19   maternal   paternal   unclear

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the probably non-dosage sensitive pericentric region of chromosome 19

 

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SCHEMATIC CYTOGENETIC DEPICTION                    
  DISCLAIMER

 

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SCHEMATIC MOLECULARGENETIC DEPICTION  

acc. to UCSC Genome Browser on Human Mar. 2006 assembly [UCSC hg18, 2006]
and available BAC-data/ array-data from cases marked *** mentioned below [MB]

 critical region ? --- 17.50 uncritical region   [26.70 centromere 30.20]   uncritical region 36.90 --- ? critical region

Below adapted for UCSC hg19, 2009

 critical region ? --- 15.20 uncritical region   [24.40 centromere 28.60]   uncritical region 32.10 --- ? critical region

 DISCLAIMER

 

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 Clinical symptoms of centromere-near proximal imbalances

 

 

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References

Cases without clinical findings (O)

 

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19-O- p13.11/ 1-1	female/ prenatal	AF	de novo	47,XX,+mar[64]/ 46,XX[24]	min(19)(:p13.11→q11~12:)  FISH-data: RP11-22G10 (22.98MB) on sSMC	cenM; subcenM, UPD-test	Amniocentesis due to advanced maternal age; normal child, APGAR 9/10/10; weight 3720g, length 54 cm; OFC 35.5 cm; at two years normal and well developed (U7 was normal)	{0} provided by Dr. Pruggmeyer, Peine, Germany
	19-O- p13.11/ 2-1	male/ prenatal	AF	de novo	47,XY,+mar[10-15%]/ 46,XX[85-90%]	min(19)(:p13.11→q12:)[2]/ min(19)(:p12→q12:)[1]	cenM; M-FISH, subcenM	Advanced maternal age; ultrasound normal; normal child born	{0} provided by Dr. Gerresheim, Bochum, Germany
	*** 19-O- p13.11/ 3-1 ***	female/ 28y	PBL (EKF- cellbank)	de novo	47,XX,+mar[60%]/ 46,XX[40%]	min(19)(:p13.11→q11:)[3]/ r(19)(::p13.11→q11::)[9]/ r(19)(::p13.11→q11: :p13.11→q11::)[2] FISH-data: RP11-22G10 (22.98MB) on sSMC aCGH: 17.50-33.59	midi; MCB; subcenM; array-CGH	normal female	{0} provided by Dr. Krüger, Rostock, Germany
	19-O- p13.11/ 4-1	female/ 43y	PBL	n.a.	47,XX,der(7)inv(7)(p22q36)inv(7)(q31.2q36),+mar[15]/ 46,XX,der(7)inv(7)(p22q36)inv(7)(q31.2q36)[67]	r(19)(:p13.1→q11:)	locus spec. probes, array-CGH	normal female, detected due to clin. abnormal daughter	{43}
	19-O- p12/ 1-1	male/ 3y	PBL cell line at ECACC DD0817	de novo	47,XY,+mar[90%]/ 46,XY[10%]	r(19)(::p12→q12::)	FISH with all available centromeric probes, cernM, subcenM, MCB; UPD test only for #16	Amniocentesis due to advanced  maternal age; clinically normal at 17m	{2} case 16 {18} case 9 {19} case 8
	*** 19-O- p11/ 1-1 ***	female/ 31y	PBL (EKF- cellbank)	n.a.	47,XX,+mar[25]/ 46,XX[75]	min(19)(:p11.1→q13.1:) FISH-data: RP11-14D17 (36.90MB) on sSMC	cenM; subcenM	genital hypoplasia	{23}case 12

 

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

 

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19- CO-1	male/ prenatal	AF	de novo	47,XY,+mar[?]/ 46,XY[?]	r(19)	different FISH probes (cep1/5/19; wcp 19)	normal	{3} case 17 {4} case 5
	19- CO-2	male/ prenatal	AF PBL	de novo	47,XY,+r[29]/ 46,XY[21] r present in 46%of PBL	r(19)	all centromeric probes	amniocentesis due to advanced  maternal age. normal at age of 18m.	{6} case 2
	19- CO-3	female/ prenatal	AF PBL	de novo	47,XX,+mar[14]/ 46,XX[8] r present in 46%of PBL	?r(19)(::p11~13.1→ q11~13.1::)*	centromeric probes, wcp 1, 5, 19	amniocentesis due to advanced  maternal age. normal at age of 3y.	{16} case 15
	19- CO-4	female/ adult	PBL	n.a.	47,XX,+mar[?100%] r present in 46%of PBL	mar(19)	n.a.	normal female; mar detected due to mar presence in unborn child.	{20} mother of case 74

 

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References

Cases with clinical findings (W)

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

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19-W- pter/ 1-1	male/ 3 m	PBL	de novo	47,XY,+mar[52]/ 46,XY[48]	min(19)(pter→p11)*	all centromeric probes; different YAC-probes	see below	{24; 29}
		normal directly after birth, ( 3550g, 51cm, OFC 36cm, Apgar 9/10);  gastrooesophagial reflux at 24 days; sonography of brain normal; at 3 m generalized muscular hypotonia; at 7.5-9y: severe  muscular hypotonia, severe mental retardation, developmental delay, dysmorphic features, strabismus, low set ears, clinodactyly, seizures, epilepsy, no walking;
	19-W- pter/ 1-2	male/ 12 year	PBL	de novo	47,XY,+mar[75]/ 46,XY[25]	mar(19)(pter→p11::)*	all centromeric probes; wcp 19, pcp 19p	similar to case 19-W-pter/1-1	{29 - case 2}
	19-W- p13.1/ 1-1	female/ prenatal	AF	de novo	47,XX,+mar[38]/ 46,XX[17]	r(19)(::p13.11→ q13.11~13.12::)[16]/ r(19;19)(::p13.11→ q13.11~13.12: :p13.11→q13.11~ 13.12::)[2]/ min(19)(:p13.11→q13.11~ 13.12:)[5]	cenM; subcenM	advanced  maternal age; no ultrasound abnormalities apart from growth retardation (1 week delayed) and the nasal bone was not visible; pregnancy ended with spontaneous abortion - no heart activity in gestational week 14+4	{17} case 19-4
	19-W- p13.1/ 1-2	female/ newborn	PBL; skin fibroblasts	de novo	47,XX,+mar[5]/ 46,XX[15]	r(19)(::p13.1→q13.1::)	midi, wcp 19, cep 1/5/19	see below	{38} case 1
		Born after normal pregnancy; intractable seizures on the first day of life. Also acquired microcephaly, severe developmental delay, a seizure disorder, and marked visual impairment. At 3y acquired microcephaly; head circumference 44 cm (<3rd centile), height 89 cm (10%), weight 13.1 kg (25%). No dysmorphic features, no organomegaly, with normal skin and extremities. Neurological examination: profound cognitive and gross motor impairment; no persistent primitive reflexes an overall developmental age of less than 4 months; normal routine blood work and cerebrospinal fluid analysis; ophthalmologic exam: optic atrophy, poor vision, and optical oscillation. Somatosensory evoked potential, brainstem auditory evoked potential, and peripheral nerve conduction were normal. Head MRI showed diffuse hyperintensity on T2-weighed images early on but there was interval maturation of myelination with only mild delay in myelination at age 3 years. There was under-operculation with simplification of the gyri in the frontal lobe, and thin corpus callosum suggesting cerebral dysgenesis. Bone films of spine showed thoraco-lumbar scoliosis.
	19-W- p13.1/ 2-1	male/ prenatal	AF; PBL;	de novo	47,XY,+mar[100%]	min(19)(pter→p13.3: :19p13.1→19q13.1:)*	WCP multiprobe device; midi; subtel 19	see below	{38} case 2
		Born by cesarean section at 37 weeks gestation as twin B of a dichorionic, diamniotic pregnancy. Twin A was a healthy male; 46,XY. The pregnancy was complicated by gestational diabetes, and ultrasound diagnosis of a left diaphragmatic hernia, probable ventricular septal defect, and small lung volume. APGAR scores were 4, 6,and 5. Birth weight 2,300 g (10th centile). Potsnatal: severe hypoxemia secondary to the diaphragmatic hernia. Echocardiogram: patent foramen ovale and tricuspid regurgitation. Abdominal ultrasound: rotated, echogenic right kidney and ectopic left kidney. Vision and hearing evaluations were normal. Other complications in the newborn period included placement of a G-tube and Nissen fundoplication for feeding aversion problems, laparoscopic repair of a small bowel obstruction, and frenotomy for treatment of tongue tie. At eight months: interactive child with microcephaly and significant delays in development. Height 62.5 cm (<3rd centile), weight 5.9 kg (<3rd centile), head circumference 39.75 cm (<3rd centile); central hypotonia, midface hypoplasia, and protuberant ears. At 2 years cognitive skills at approximately the 12-month level and motor skills at the 10-month level. Height 74.5 cm (<3rd centile), weight 9.4 kg (<3rd centile), head circumference 43.5cm(<3rd centile); moderate thoracic scoliosis and central hypotonia; still exhibited significant feeding aversion.
	19-W- p13.1/ 3-1  °	male/ 5 year	PBL (EKF- cellbank)	n.a.	47,XY,+mar[19]/ 46,XY[11]	min(19)(:p13.11~13.12→q12:)	cenM; subcenM	developmental delay	{0} provided by Dr. Belitz  Berlin,  Germany
	19-W- p12/ 1-1	male/ 1 w	PBL	de novo	48,XY,+marx2[100%]	min(19)(:p12→q12:)x2	cenM; subcenM	see below	{27}case 30
		full term pregnancy (G4,P2; G2 miscarriage, G3, legal abortion) at birth weight 2800g, lenght 49cm, OFC 34cm; (OFC at 11m 43cm) facial dysmorphism, hypertelorism, low set dysmorphic ears, preauricular fistula, high palate, flat wide root of the short nose; flat round face, narrow palpebral fissures, microretrognathia, long philtrum, open mouth, high line of hair, spars hair spare eyebrows, horizontal fissures, epicanthus, systolic murmur, heart defect, severe muscular hypotonia, decreased reflexes, short neck, mild lymphoedema at hand and feet, pes planus, ventriculomegalia, severe developmental delay, small scrotum, cryptorchidism
	*** 19-W- p12/ 2-1 ***	male/ 3 m	PBL (EKF- cellbank)	n.a.	47,XY,+mar[60-90%]/ 46,XY[40-10%]	min(19)(:p12→q12:) size in p 2.59MB (= position 25.91 MB) , in q 2.3 MB (= position 32.4MB)	MCB; subcenM midi, array-CGH (Agilent 244k-chip)	see below	{0}provided by Dr. Altus, Magdeburg, Germany {26}
		born in week 31 spontaneously, weight 2060g (93centile), length 42,5cm (58 centile), OFC 31.5 cm (92 centile) , APGAR 7/8/8hyperbilirubinamia, subluxation of hip joint, Pes calcaneovalgus congenitus, periodic breathing, stridor cong, feeding problems. at 3 months: extreme restlessness, nearly opstotone posture; OFC now at 10. centile; at 5m: hyperexitability, developmental delay
	19-W- p12/ 3-1	male/ 16y 8 m	PBL	n.a.	47,XY,+r1[?%]/ 47,XY,+r2[?%]	r(19)(::p1?2→q11::)*/ r(19)(::p11→q1?2::)*	cep probes wcp 19, centromere near cosmids	see below	{28}
		overweight, mentally retarded with macrocephaly, hypertelorism, antimongoloid slants, epilepsy (convulsive seizures with or without hyperthermia from 1y)
	19-W- p12/ 4-1	female/ 15y	PBL	de novo	47,XX,+r[100%]	r(19)(::p12→q12::) aCGH: 23.12-33.29MB	M-FISH, diff. FISH-probes, aCGH	see below	{45}
		As newborn child seemed normal. Later in childhood, developmental delay, particularly of language skills. At 15y height >95th centile, high forehead, down-slanting palpebral fissures, wide diastema between upper incisors, high palate, short fraenulum of the upper lip, prominent lips and scoliosis, long and tapering fingers, fifth finger campodactyly, hallux valgus, fifth toe clinodactyly, pes planus. Overall neuropsychological picture: borderline intelligence with specific cognitive deficits in the processing of verbal information as well as learning disorders. Brain magnetic resonance imaging: enlarged cisterna magna with slight hypoplasia of the basal part of the cerebellar hemispheres as well as of the inferior vermis; the posterior fossa was normal.
	*** 19-W- p12/ 5-1  ° ***	male/ 13y (EKF- cellbank)	PBL	de novo	47,XY,+mar[23]/ 46,XY[7]	min(19)(:p12→q13.11~13.12:) size in p: RP11-22G10 in subcenM present on sSMC (22.98 MB - no signal in p on array), in q according to array: sSMC goes to 36.3 MB	cep; wcp; subcenM; array-CGH	see below	{0} provided by Drs. Prager and Junge, Dresden, Germany
		Normal pregnancy and birth. At birth weight 4080g, length 52cm, APGAR 9/10; OFC 37cm; sitting with 6 months, walking with 13 months, speaking with 3 years. Developmental delay noticed from ~5 years. Anxious and impulsive behavior,
	19-W- p12/ 5-2  °	male/ 4y	PBL	n.a.	47,XY,+mar[50%]/ 46,XY[50%]	min(19)(:p12→q13.1?1:)	cenM; subcenM	developmental delay	{0} provided by Dr. Albrecht, Essen, Germany
	19-W- p12/ 5-3  °	male/ 4y 10m	PBL	n.a.	47,XY,+mar[44-60%]/46,XY[54-40%]	mar(19)(:p12→q13.11:) positions: 19.80 to 38.21	aCGH	see below	{41;44}
		normal pregnancy apart from oligoamnion in last month. weight length and APGAR normal at birth; Asperger syndrome = autism; mild hypotonia; milestones in development delayed
	19-W- p12/ 6-1	female/ 7y	PBL	n.a.	47,XX,+r[3]/46,XX[7]	r(19)(::p12→q13.2::) aCGH: 23.73 to 43.47	different FISH-probes; aCGH	global developmental delay	{46} case 11
	19-W- p11/ 1-1  °	male/ 5y	PBL	de novo	47,XY,+mar[?]/ 46,XY[?]	min(19)(:p11→q13.11:) FISH-data: 26.7-at least to 33.3MB	cenM; subcenM	see below	{17} case 19-1
		Pre- and postnatally no clinical signs before the age of 1.5 years; then slight developmental retardation: first speech with 18 months; walking with 22 months; weight: 8.82kg (1.5y); height 81cm (1.5y); head circumference 49.7cm (1.5y); minimal cerebral dysfunction (MCD) at age of 4; no severe clinical signs.
	19-W- p11/ 1-2  °	n.a./ 2y	PBL	de novo	47,+mar[100%]	min(19)(:p11→q13.11:)* size  ~0.4MB	n.a.; subcenM with 3 BACs; array CGH	see below	{25} case 20
		Metopic craniosynostosis; ventricular septal defect (VSD); strabismus; significant developmental delay; not rolling or sitting at 7 months of age; “not talking” at 27 months of age.
	19-W- p11/ 2-1	female/ 4.5y	PBL	de novo	47,XX,+r[30%]/ 46,XX[60%]	r(19)(::p11→q13.32::)	midi	see below	{0} provided by Dr. Zvi Borochowitz; Israel
		severely affected with mental retardation, microcephaly and dysmorphic features including small ears, anti-mongolian slant, broad faces, bulbous nose, large cheeks and somewhat furrowed forehead
	19-W- p1?0/ 1-1	female/ 49y	PBL	n.a.	47,XX,+r[7]/ 46,XX[18]	r(19)(::p1?0→q13.42::)*	CGH; cep1/5/19; wcp 19; pcp19p, pcp19q, subtel  19q	see below	{5}
		walking at age of 2y, speech at 4-5y; residential care since age of 16y.  At age of 71y height of 132 cm, head circumference of 52.5 cm, blood pressure of 180/110 mm Hg, poor periphera1 circulation, earIy hypertensive changes in both optic fundi, poor vision, Upward slanting palpebral fissures, large tongue, protruding lower lip, normal pa1mar creases, normal female genitalia, and deep set toe nails; radiological signs of subluxed, osteoarthritic hip joints. Moderate to mild learning disability.
	19-W- p10/ 2-1	see McCl-19-W-p10/1-1							{7}
	19-W- p10/ 3-1  °	male/ 14y	PBL	de novo	47,XY,+mar[100%]	r(19)(::p10→q13.2::)*	M-FISH cep probes; CGH	see below	{22}
		Born at 39 weeks gestation after a pregnancy with gestational diabetes and a delivery reported to be prolonged; birth weight was 3950g. Hypertonia was noticed from birth and continued throughout the first 6 months of life; Significant for motor and cognitive developmental delay identified from early infancy. At 31, 36 and 60 months of age he had the developmental age of 18, 20 and 30 months, respectively. He gained speech skills at 6 years of age and currently, his cognitive skills are very limited, with poor learning and speech abilities; limited social interactions; mild dysmorphic features including macrocranium, round face, upslanting eyes and thick auricles Brain CT and MRI performed revealed cortical atrophy, partial agenesis of the corpus callosum and mild changes in the white matter in the occipital lobes; several generalized tonic-clonic seizures started at 1 year of age. EEG and video-EEG performed at the first and third years of life showed waves and spikes from foci in both hemispheres with a few generalized bursts, and slow background activity. Growth pattern was characterized by height at the 50th percentile over the first 2 years of life and along the 90th percentile thereafter, with head circumference at the 90th percentile from infancy; most prominent growth feature was a remarkable weight gain: BMI 33.5, 44, 46 and 51 at 5, 8, 10 and 12 years of age, respectively. Subsequent to morbid obesity, he developed several co-morbidities:(1) hypercholesterolemia (2) moderate elevations in liver transaminase levels, (3) hyperuricemia that responded to a short-term treatment with allopurinol; (4) a mild degree of pulmonary hypertension, documented by echocardiography; and (5) Pickwickian syndrome, manifested by night snoring, daytime somnolence and episodes of sleep apnea. At about 13 years of age the patient started pubertal maturation, and currently (at 14 years of age) he is in Tanner pubertal stage.

 

 

 

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

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19- CW-1	female/ 5y	PBL	de novo	47,XX,+mar[36]/ 46,XX[54]	r(19)	FISH probe  wcp 19	see below	{12}
		Normal pregnancy and birth; weight: 4870g, length 55g, OFC 37.5g →all >95th centile;  At 11m developmental delay; at 0m hypotonia, gross motor delay; at 5y still weight, lenght and OFC  >90. centile; mild dysmorphism including bifronatal narrowing, prominent glabella, deep-set eyes, bulbous nasal nip, prominent lower jaw, short fat hands with long , tapering fingers; mild hypotonia, slightly hunched back;
	19- CW-2	female/ 0.5y	PBL	de novo	47,XX,+mar[60%]/ 46,XX[40%] in both monozygotic twins	mar(19)	FISH probe  wcp 19	see below	{13}
		Twins born in week 35 of gestation, mild neonatal jaundice; normal at birth; at 5m twin II had a generalized tonic-clonic seizure associated with fever; at 6m other similar seizures without feaver; at 22m she was found dead in her cot and was presumed to have had a prolonged seizure.  In Twin I eyelid twitching and flickering at 6m and seizures subsequently. developmental delay occurred and lost of ability to walk unaided at 18m. OFC always on 90. centile; abnormal EEG; developmental delay; died at 4y8m due to a prolonged status epilepticus (4h)
	19- CW-3	male/ prenatal	AF	de novo	47,XY,+mar[27]/ 46,XY[23]	r(19)	D1Z7/D5Z2/D19Z3; wcp 19	see below	{14} case 3
		Amniocentesis due to abnormalities identified on ultrasound: oligohydramnios, clubfoot and increased nuchal thickness. parents elected to terminate the pregnancy.
	19- CW-4	female/ 1y	PBL	de novo	47,XX,+mar[40%]/ 46,XX[60%]	r(19p)	M-FISH; D1Z7/D5Z2/D19Z3; wcp 19; pcp19p; pcp19q; sub-telomere 19p 19q12 probe RP11-375D11	see below	{15}
		normal pregnancy, at birth weight: 3055g, length 49cm, OFD 33cm; APGAR 5/7; redundant skin, two cavernous angiomas on the back, hypertrophic clitoris, congenital hip dysplasia which required orthopedic correction, cutis marmorata, peripheral cyanosis, joint hyper laxity, axial hypotonia, transient hypocalcemia and hypoglycemia. Att 12 months, no head and trunk control, severely hypotonic, thin hair, high and prominent forehead, round face, sparse eyebrows, downward slanted palpebral fissures, hypertelorism, depressed mid face, low nasal bridge, short nose, anteverted nares, chubby cheeks, long philtrum, protruding tongue, prominent lower lip, receding chin, low-set asymmetric and dysmorphic ears with prominent helix, spaced nipples, and tapering fingers (Fig. 1). Brain MRI disclosed the enlargement of the lateral ventricles with moderate to severe cortical atrophy.
	19- CW-5	female/ postnatal	PBL	n.a.	47XX,+mar[?%]	min(19) 44.9 MB size	array-CGH	see below	{39} 1 case
		ophthalmologic disease
	19- CW-6	n.a./ prenatal	AF	de novo	47,+mar[?%]	r(19)	n.a.	abnormal sonography; TOP	{40} 1 case
	19- CW-7	female/ 1m	PBL	de novo	47,XX,+mar[92]/ 46,XX[83]	mar(19)(:p11→12:) mlpa p181x3	MLPA; cep 1/5/19	abnormal facial appearance	{0} provided by Dr. A. Delicado Navarro, Spain
	19- CW-8	female/ 2y	PBL	n.a.	47,XX,+r[100%]	r(19)	SKY	multiple congenitals abnromalities	{48} case F0628560
	19- CW-9	female/ 12y	PBL	n.a.	47,XX,+mar[100%]	min(19)	SKY	mental retardation	{48} case F0642312

 

 

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References

Cases with unclear clinical correlation (U)

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19-U- 1	female/ prenatal	AF	de novo	47,XX,+mar[45]/ 46,XX[10]	min(19)(:p12→q13.1:)	M-FISH; cenM; MCB	see below	{1} case 28
		Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; pregnancy terminated
	19-U- 2	male/ prenatal	AF	de novo	47,XY,+mar[38]/ 46,XY[17]	r(19)(::p13.11→ q13.11-12::)[16]/ r(19;19)(::p13.11→ q13.11-12: :p13.11→q13.11~ 12::)[2]/ min(19)(:p13.11→ q13.11-12:)[5]	cenM; subcenM	see below	{0} provided by Dr. Mazauric, Düsseldorf, Germany
		Amniocentesis due to advanced  maternal age; no ultrasound abnormalities in week 15; spontaneous abortion after amniocentesis
	19-U- 3	male/ prenatal	AF	de novo?	47,XY,+mar[100%]	r(19)(::p12→q12::)	midi	n.a.	{9} case 4
	19-U- 4	male/ prenatal	AF	de novo	47,XY,+r[17%]/ 46,XY[83%]	r(19)	centromeric probes and wcp	pregnancy terminated; autopsy result normal	{10} case 5
	19-U- 5	female/ prenatal	AF	de novo	47,XX,+mar[10%]/ 46,XX[90%]	min(19)(:p13.11→q12:)	cenM; subcenM	Amniocentesis due to advanced  maternal age; no ultrasound abnormalities; pregnancy was terminated - no additional information available	{0} provided by Dr. Klein, Butzbach, Germany
	19-U- 6	male/ prenatal	AF	de novo	47,XY,dup(21)(q22.2q21.1),+r[18]/ 46,XY,dup(21)(q22.2q21.1)[32]	r(19)(::p13.11→q13.2::)* sSMC derived from a maternal chromosome 19	different FISH probes, micro satellite analysis; UPD-test	see below	{8} case 3 {42}
		Amniocentesis due to advanced  maternal age; Baby born by cesarean section at 40th week without complications, with hypotonia, dysmorphic craniofacial features including microcephaly, hypertelorism, upward slanting palpebral fissures, deep palmar and plantar crease; delayed myelinisation, psychomotor development moderately delayed at 9m. No Down syndrome features, which is in concordance with the lack of the DSCR.
	19-U- 7	female/ prenatal	AF (EKF- cellbank)	de novo	47,XX,+mar[10]/ 46,XX[30]	min(19)(:p13.11→q12:)  FISH-data: 26.7-at least to 33.3MB	cenM; subcenM; UPD-test	see below	{23} case 13
		possible hypotrophy in US, parents 31y and non-consanguineous. Already one healthy 4 y old girl. Amniocentesis due to abnormal maternal screening (1/100); pregnancy terminated, no autopsy but fetus without abnormalities
	19-U- 8	n.a./ prenatal	AF	de novo	47,+mar[100%]	r(19)	M-FISH; wcp 19	abnormal in 1st ultrasound. hydramnios	{21} case 4
	19-U- 9	n.a./ prenatal	AF	de novo	47,+mar[100%]	r(19)	M-FISH; wcp 19	maternal serum screen test; TOP	{21} case 12
	19-U- 10	male/ prenatal	chord blood	de novo	47,XY,+mar[28]/ 46,XY[4]	r(19)(::p13.1→q13.1::)[17]/ r(19;19)(::p13.1→q13.1: :p13.1→q13.1::)[4] FISH-data: breaks between 10.61-22.66 and 48.31-57.56 MB	M-FISH; subcenM, PCL-FISH	enhanced nuchal translucency, TOP	{0} provided by Dr. Seher, Ankara, Turkey
	19-U- 11	female/ prenatal	AF	de novo	47,XY,+mar[34%]/ 46,XY[66%]	r(19)(::p11.1→q12::)	M-FISH; subcenM; UPD-test	advanced maternal age, patient lost during follow up	{0} provided by Drs. Wagner and Stibbe, Hannover, Germany
	19-U- 12	female/ prenatal	AF	de novo	47,XY,+mar[40%]/ 46,XY[60%]	min(19)(:p11.1→q13.1~ 13.2:)[16]/ r(19)(::p11.1→q13.1~ 13.2::)[8]/ r(19;19)(::p11.1→q13.1~13.2: :p11.1→q13.1~13.2::)[1]	cenM-FISH; subcenM	advanced maternal age, patient lost during follow up	{0} provided by Drs. Wagner and Stibbe, Hannover, Germany
	19-U- 13	n.a./ prenatal	AF	n.a.	47,+mar[17%]/ 46[83%]	r(19)	wcp19; cep19	Advanced maternal age. no further information available TOP	{37} case 13
	19-U- 14	n.a./ prenatal	AF	n.a.	47,+mar[60%]/ 46[40%]	min(19)(:p12→q13.1:) aCGH: 24.08-40.50	wcp19; cep19, subcenM; aCGH	n.a.	{0} provided by J. Melo, Coimbra, Portugal
	19-U- 15	female/ postnatal	PBL	n.a.	47,XX,+mar[?%]	der(19)t(18;19)	array-CGH	psychomotor disorder	{39} 1 case
	19-U- 16	male/ prenatal	AF	n.a.	47,XY,+mar[100%]	min(19)(:p13.11→q11:)	cenM, subcenM	n.a.	{0} provided by Dr. Alves, Porto, Portugal
	19-U- 17	n.a./ prenatal	AF	n.a.	47,+mar[100%]	min(19)(:p12→q12:) aCGH: 33.10-33.59	cenM; subcenM; array-CGH	amniocentesis due to advanced maternal age; no US abnormalities. No further info available	{0} provided by Dr. Eiben, Oberhausen, Germany
	19-U- 18	female/ prenatal	AF	n.a.	47,+mar[?100%]	mar(19)	SKY	n.a.	{48} case F0534481

 

 

 

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References

Cases with neocentromeres (N)

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result grade of mosaicism	final result of the sSMC	test methods	clinical symptoms	reference
	19-N- pt13.2/ 1-1	n.a./ 11m	PBL	n.a.	47,+mar[30%]/ 46[70%] acc. to FISH	?inv dup(19)(pter→q13.2: :q13.2→pter)	aCGH; RP11-19I2	developmental delay, short stature	{47} case 8

 

 

N-Cases with similar imbalances NOT caused by sSMC (N-IMB)

 

	case no.	gender/ age at diagnosis	studied  material	de novo/  inherited	GTG-banding result and FISH result incl. grade of mosaicism	test methods	clinical symptoms	reference
	19-N- IMB- pter/ 1-1 to 1-2	see {30; 31}						{30; 31}
	19-N- IMB- qter/ 1-1 to 1-13	see {32-36}						{32-36}