FISH
SMALL SUPERNUMERARY MARKER CHROMOSOMES- sSMC McClintock -
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"In one of her seminal contributions Barbara McClintock describes the mechanism leading to the formation of ring/deleted chromosomes in maize and the aberrant mitotic behaviour leading to 'variable mutant characteristics'. This mechanism, a break within the centromere together with a break in either the long or the short arm, creating a small ring, has been called "centromere misdivision"; these authors propose that this be referred to as "the McClintock mechanism". McClintock also describes pachytene configurations in microsporocytes, showing that although the normal, deleted and ring chromosomes may synapse, the ring is also seen with the centromeric region attached to a non-homologous bivalent." (cited from Mantzouratou et al., Molecular Cytogenetics 2009, 2:3)
| 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 | ||
| McCl- 01-N- p32/ 1-1 |
male/ 38y |
PBL/ fibro- blasts |
n.a. | 47,XY,del(1)(p32p36.1), +mar1[87]/ 47,XY,del(1)(p32p36.1), +mar2[10]/ 46,XY,del(1)(p32p36.1)[3] (fibroblasts: 95/5/0; plus a t(X;4)(q23;q13)) |
mar1 = r(1)(::p32→p36.1::)/ mar2 = r(1)(::p32→p36.1: :p23→p36.1::) |
pan-centromeric probe, telomeric probe, wcp1 probe; UPD-test | infertility and oligospermia; otherwise normal male | {1-5} | ||
| McCl- 01-N- q23/ 1-1 |
male/ prenatal |
AF | de novo | 47,XY,del(1)(q23q32), +mar[20] |
r(1)(::q23→q32::) "dynamic mosaic" i.e. variants of sSMC were detected but not characterized in detail |
wcp1; cep1/5/19; all centromere probe; | Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated. | {3-6} | ||
| McCl- 02-O- p12/ 1-1 |
male/ adult |
PBL | de novo | 47,XY,del(2)(p12p11.1), +mar[100%]* |
r(2)(::p12→p11.1::) FISH-data: RP11-316G9 = AC009958.3 (89.6 MB) and RP11-294I29 = AQ508381 (88.9MB) on sSMC |
cen2, wcp2, YACs as specified in {11} | Man was studied due to a child with a phenotype resembling Down-syndrome; child had karyotype 46,XY,del(2)(p10p12), | {0} {8} |
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| McCl- 02-N- p21/ 1-1 |
male/ 14y |
PBL | de novo | 47,XY,del(2)(p21p11), +mar[100%] |
r(2)(::p21→p11::) | wcp2, pan-centromeric probe; telomeric probe | see below | {3; 9-11} | ||
| moderately mental retarded, at 32y weight and OFC at 25. centile; narrow forehead, broad supraorbital ridges, large mouth, marked hyperkyphosis, moderately hyperactive, IQ = 50. | ||||||||||
| McCl- 02-N- q35/ 1-1 |
female/ postnatal |
PBL (EKF- cellbank) |
n.a. | 47,XX,del(2)(q22q32.2), +r(2)(q22q32.2)[81]/ 46,XX, del(2)(q22q32.2)[9] |
n.a. | n.a. | mental retardation | {12} 1case | ||
| McCl- 03-W- p11/ 1-1 |
male/ 26y |
PBL/ fibro- blasts |
de novo | 47,XY,del(3)(p11q11), +mar[28]/ 46,XY,del(3)(p11q11)[12] mar present in 100% of skin fibroblasts |
min(3)(:p11→q11:) | wcp3; cep3 | see below | {13; 14; 15 case 1} | ||
| The male was considered to have borderline mental retardation. and was detected due to his newborn daughter with developmental delay, hypertelorism, epicanthus. She inherited only the del(3) chromosome. Neocentromere formation in 3q26 on del(3) chromosome. | ||||||||||
| McCl- 04-W- p15.3/ 1-1 |
male/ prenatal |
AF | de novo | 47,XY, del(4)(p15.3q21.1), +r[96]/ 46,XY,del(4)(p15.3q21.1)[4] |
r(4)(::p15.3→q21.1::) | cep 4, sub-telomeric probe 4q; WHS probe | see below | {16} | ||
| Amniocentesis due to ultrasound detection of advanced nuchal translucency, echogenic bowel, short femurs, mild ventricular dilatation; IUGR at 5. centile; at week 32 oligohydramnion; at week 33 no fetal movements and intrauterine death confirmed at week 34; on delivery bay 640g (<0.4 centile) and macerated; detectable were anal atresia, neck webbing, umbilical cord with two vessels; | ||||||||||
| McCl- 04-W- p12/ 1-1 |
female/ adult |
PBL | n.a.; same mar imbalanced in child | 47,XX,+mar[67%]/ 46,XX[33%] |
47,XX,del(4)(p12q10), +r(4)(::p12→q10::)[66%]/ 46,XX,del(4)(p12q10)[33%]* size 4.4 MB |
centr. probes, centr.-near probes; array CGH | see below | {17} {18} case 7 |
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| child with mild speech delay; no dysmorphic features; normal motor development; Mother is intellectually normal with unilateral ear anomalies and mild visual deficiencies. | ||||||||||
| McCl- 04-N- q22.1/ 1-1 |
male/ 17y |
PBL/ fibro- blasts |
de novo | 47,XY,del(4)(q21.1q21.3), +mar[75%]/ 46,XY,del(4)(q21.1q21.3)[25%]* |
r(4)(::q21.1→q21.3::)* sSMC derived from maternal chromosome 4 |
midi; telomeric probes, YACs; UPD-test | see below | {19; 3-5} | ||
| neonatal eczema, multiple infections; studied due to Hyper-IGE syndrome with recurrent infections (HIES); motor, language, social and developmental milestones of patient delayed; mother of patient borderline to mental retardation, autism. | ||||||||||
| McCl- 5-W- p13/ 1-1 |
male/ 27y |
PBL | n.a. | 47,XY,del(5)(p13q10), +r[68]/ 46,XY,del(5)(p13cen)[2] |
r(5)(::p13→q10: :p13→q10::) |
cep 1/5/19; YAC 897G2 | see below | {20} | ||
| Birth weight 3500g (50th centile), OFC 38cm (>95. centile); length 50cm (25. centile); square asymmetric skull, plagioturricephaly, facial asymmetry, hypertelorism, epicantal folds, short and broad nose, long, deep philtrum, microretrognathism, high palate, low-set abnormal ears, clinodactyly 5, simian crease, hypotonia, omphalocoele, inguinal hernias, club feet; at 20m weight at 90. centile OFC >97. psychomotor development delayed. | ||||||||||
| McCl- 5-W- p11/ 1-1 |
male/ prenatal |
AF, PBL |
de novo | 47,XY,del(5)(p11p13), +mar[100%] after array: 47,XY,der(5)(pter→p15.31: :pter→p14.3::p11→qter), +r(5)(::p11→q13.2::) |
r(5)(::p11→q13.2::) array: 5p15.33-p15.31 (131,945-6,267,160)x3, 5p14.3-p13.2 (21,438,495- 36,736,934)x1, 5p12-p11 (42,529,343- 45,908,725)x3 |
BAC-FISH, aCGH | amniocentesis due to advanced maternal age; normal male at birth and at 1.5y | {54} | ||
| McCl- 06-O- p22.3/ 1-1 |
male/ 43y |
PBL | n.a. | 47,XY,del(6)(p10p22.3), +r(6)(::p10→p22.3::)[100%] |
r(6)(::p22.3→q10::)* | wcp6, cep 6, subtel 6p and 6q | normal male apart from infertility | {21} {22} case 10 |
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| McCl- 06-O- p11.2~ p11.1/ 1-1 |
female/ 37y |
PBL | de novo | 47,XX,del(6)(p11.2~p11.1q12), +r(?6)[80%]/ 46,XX[20%] |
r(6)(::p10→q12::)[60%]/ r(6)(::p11.2~p11.1 →q12::)[20%] |
midi/ subcenM |
normal, but two abnormal children with mar | {0} provided by Dr. Spranger, Bremen, Germany) | ||
| McCl- 06-O- p10/ 1-1 |
female/ 30y |
PBL | n.a. | 47,XX,del(6)(p10q13), +r(6)[?%]/ 46,XX[?%] |
r(6)(::p10→q13::) array: 77.23-96.63MB |
MCB, aCGH | normal, but one abnormal children with mar | {55} mother of patient 2 | ||
| McCl- 06-N- q16.2/ 1-1 |
male/ adult |
PBL | de novo? | 47,XY,t(4;15),del(6)(q16.2q22.2), +r(6)(::q16.2→q22.2::)[100%] |
n.a. | all centromeres, wcp probes, sub-telomere 6q | mar detected due to phenotypically abnormal child of propositus; child had karyotype 46,t(4;15),del(6)(q16.2q22.2)[100%] | {5; 23-24} | ||
| McCl- 08-O- p11.1/ 2-1 |
male/ adult |
PBL | de novo | 47,XY,del(8)(p11.1q12.1),+r(8)(p11.1q12.1)[18]/ 46,XY[2] |
r(8)(::p11.1→q12.1::)* neocentromere in 8p22 in der(8) |
array-CGH, cep 8 | normal male, sSMC detected due to child with clinical abnormalities due to lacking sSMC | {25; 53} | ||
| McCl- 09-N- q31/ 1-1 |
female/ adult |
PBL | n.a. | 47,XX,del(9)(q31q33),+r(9)(q31q33)[60%]/ 46,XX,del(9)(q31q33)[40%] |
r(9)(::q31→q33::) | array CGH; BAC FISH | mild degree of mental retardation (IQ 69); sSMC detected due to child with a 46,XY,del(9)(q31q33)[100%] and mild psychomotor retardation | {30} | ||
| McCl- 10-W- p11.23/ 1-1 |
male/ 4y10m |
PBL | inv dup (13 or 21) paternal derived | 48,XY,del(10),+r(?10), +inv dup(acro)[100%] double rings in 4-8% of the cells |
del(10) = der(10)(pter→p11.23: :q23.2→qter) r(?10) = r(10)(::p11.23→q23.2::) inv dup(acro) = inv dup(13or 21) |
cep10, 13/21; 14/22; 15; 5 different alpha sat.- probes; satIII probe | see below | {3-4; 10; 31-39} | ||
| developmental delay at 4y, delayed speech development, normal motor activity, not dysmorphic; height, length and HC ~25. centile | ||||||||||
| McCl- 10-N- q11/ 1-1 |
female/ 1w |
AF/ fibro- blasts |
de novo | 47,XX,del(10)(q11q23),+mar[62%]/ 46,XX,del(10)(q11q23)[38%] (sSMC in 80% of fibroblasts) |
?min(10)(:q11→q23:) (without detectable telomeres) |
alpha-, beta-satellite satIII,telomeric, all wcp, YAC-probes (not specified) | see below | {26} case 8 {3-5, 10} |
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| mental retardation and/or developmental delay or structural anomalies detected at birth | ||||||||||
| McCl- 11-O- p15.1/ 1-1 |
female/ newborn |
PBL fibro- blasts |
maternal | PBL: 47,XX,del(11)(p11.1p15.1), +r(11)(p11.1p15.1)[70%]/ 46,XX,del(11)(p11.1p15.1)[30%] In Fibroblasts: marker in 50% |
cep 11 | see below | {40} | |||
| severely dysmorphic; Turner-like phenotype with classical bilateral aniridia, microcephaly, Fallot tetralogy; mother with aniridia as well - here mar in 70% of the blood cells; otherwise normal | ||||||||||
| McCl- 11-N- p11.2/ 1-1 |
female/ adult |
PBL | n.a. | 47,XX,del(11)(p11.12p11.2),+mar[100%] | r(11)(::p11.12→p11.2::) | n.a. | normal - sSMC detected due to clinical abnormalities in a child | {5; 7} | ||
| McCl- 12-U p13.1/ 1-1 |
female/ 3m |
PBL | maternal | 47,XX,del(12)(p13.1→q10),+r[100%] | r(12)(::p13.1→q10::) | wcp12 | mother normal?; child? | {27} | ||
| McCl- 13-N- p12.3/ 1-1 |
male/ 29y |
PBL | n.a. | 47,XX,del(13)(q12.3q22), +mar[97]/46,XX,del(13)(q12.3q22)[3] |
r(13)(::q12.3→q22::) | wcp, array-CGH | normal male; fertility problems | {51} | ||
| McCl- 13-N- p21.31/ 1-1 |
female/ 32y |
PBL | de novo | 47,XX,del(13)(q21.32q22.2), +mar[100%] |
r(13)(::q21.31→q22.2::) | midi; telomeric probe | normal female; sSMC detected due to 3 miscarriages | {4-5, 29-30; 42} | ||
| McCl- 13-N- q31.1/ 1-1 |
male/ 1m (?) |
PBL | de novo | 47,XY,del(13)(q31.1q32.3), +r(13)(::q31.1q32.3::)[50%]/ 46,XY,del(13)(q31.1q32.3)[50%] |
r(13)(::q31.1→q32.3::) | BAC-probes | see below | {5; 28} | ||
| moderate intellectual disability associated with distinctive hand malformations (hypoplastic and angel-shaped middle phalanges) and partial growth hormone (GH) deficiency at 13 y | ||||||||||
| McCl- 16-W- p10/ 1-1 |
female/ 23y |
PBL | n.a. | 47,XX,del(16)(p10q13), +r(16)(::p10→q13::)[100%]* | n.a. | n.a. | see below | {43} | ||
| mild general hypotonia, HC 51cm = very small; bow shaped mouth, abnormal posteriorly rotated ears; apart from that normal; detected due to a malformed child without the mar but with the del(16) chromosome | ||||||||||
| McCl- 17-O- p11.2/ 2-1 |
female/ 26y |
PBL/ fibro- blasts |
de novo | 47,XX,del(17)(p11.2q10) +min(17)(:p11.2→q10:) [89]/ 46,XX,del(17)(p11.2q10)[11] in fibroblasts mar in 62/72 |
n.a. | n.a. | normal female; mar detected due to a daughter with partial del. and son with partial dup of 17p11.2-q10 | {44- 46} | ||
| McCl- 17-U- p10/ 1-1 |
female/ 82y |
PBL skin fibro- blasts |
de novo | 48,XX,del(17)(p10q11.2),+r[2%]/ 47,XX,del(17)(p10q11.2),+r[~75%]/ 47,XX,del(17)(p10q11.2),+r(dic)[12%]/ 47,XX,del(17)(p10q11.2),+mar[~5%]/ 46,XX,del(17)(p10q11.2)[6%]* similar in blood and fibroblasts; |
marker derived from (17)(p10q11.2) | centromeric probe for chromosome 17 | see below | {47} | ||
| no congenital malformations; suffering from neurofibromatosis type 1 since age of 40y; neither her parents nor her children had NF1. Children with normal karyotypes. | ||||||||||
| McCl- 19-W- p10/ 1-1 |
male/ 1m(?) |
PBL | maternal 47,XX,del(19) (p10q13.2),+r(19) |
47,XY,+r[100%] | r(19)(::p10→q13.2::)* | FISH probe wcp 19 | see below | {48} | ||
| Delivery in week 37 because of maternal blood hypertension; birth weight 2280g; overweight syndrome at 3-4y → every mensurartions were more than 3S.D. except for the length. Additionally macrocephaly, hypertelorism, antimongoloid slants, bluish ring around the eyes, globular prominent nose, abnormal mouth, large ears, arms and legs short and podgy, mental retardation (DQ=69) | ||||||||||
| McCl- 22-O- q11.1/ 1-1 |
female/ 44y |
PBL | n.a. | 47,XX,del(22)(p11.1q11.2) +mar[16]/ 46,XX,del(22)(p11.1q11.2) |
r(22)(::q10q11.2::) | DiGeorge CR-probe; array-CGH | normal female; mar detected due to repeated children with heart defects | {52} | ||
| McCl- 22-W- q11.2/ 2-1 |
male/ infant |
PBL | maternal 47,XX,del(22)(q11q11.2), +r(22)(q10q11.2) |
47,XY,+mar[100%] | r(22)(::q10q11.2::) | cep probes; TUPLE1 probe | CHARGE association | {49} | ||
| McCl- 0X-W- p21/ 2-1 |
female/ 1y |
PBL | de novo | 47,X,del(Xq),+r[20%]/ 46,X,del(Xq)[80%] in fibroblasts. 40/10 |
del(X) = der(X)(pter→q21.1: :p21→pter) r = r(X)(::p21→ q11~12::) |
cep X; wcp X; pericentric probes; STS, KAL; UBE1XIST specific probe | see below | {50} | ||
| pregnancy and birth normal; birth weight 30. centile; length 10. centile; OFC 25. centile; syndactyly of right finger 3 and 4 and left toes 4 and 5; cardiac murmur due to ventricular and artrial septal defect and patent ductus arteriousus plus pulmonary stenosis; agenesis of corpus callosum, mild cerebral ventricular dilatation; a t 1y severely handicapped, no speech, hypotonia, broad face, short neck, prominent forehead, telecanthus, convergent strabismus, small abnormal nose, prominent inverted V-shaped upper lip, short philtrum, low set and mildly posteriorly rotated ears | ||||||||||