A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH) ~

Rauch A, Pfeiffer RA, Trautmann U, Liehr T, Rott HD, Ulmer R. A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH). Clin Genet 1992: 42: 84-90. In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for partial trisomy 21 in an adolescent with minor features of Down’s syndrome. Moreover, an i( 18p) in a mentally retarded dysmorphic child and an idic( i 5) in a child with Fallot tetralogy was confirmed. In a child with r(21). a supernumerary marker was shown to be derived from no. 21, while in the mother an additional marker idic(22) was noted.

A. Rauch, R A. Piemet, U. Trautmann, T. Liehr, H. D. Rott and R. Ulmer lnstitut fiir Humangenetik der Friedrich-Alexander Universitat Erlangen-Nknberg, FRG

Key words: fluorescence in situ hybridization marker chromosomes marker chromosomes 3, 11. 15, 18, 21. 22. X

-

Prof. Dr. R. A. Pfeilfer, Schwabachanlage 10, D 8520 Erlangen, FRG Received 18 December 1991. revised 27 accepted for publication 6 April 1992

Small supernumerary marker chromosomes have been found in 0.01-0.05Y0 of liveborn infants (Buckton et al. 1980) and in 0.1% (Benn & Hsu 1984) and 0.019% of fetuses (Warburton 1984). Up to now, the identification of marker chromosomes has been limited to morphological or staining characteristics. As they are mitotically stable, they should consist mainly of pericentric chromatin and therefore contain few, if any, active genes. However, the diversity of markers is emphasized by the observation that in de novo cases the rate of phenotypic abnormalities was shown to be increased (Warburton 1984), thus suggesting functional chromatin, although they were thought to be genetically inert when regularly transmitted (Martin et al. 1986). Moreover, in order to explain unusual manifestations, imprinting and isodisomy may be taken into account (Dahoun-Hadorn & Delozier-Blanchet 1990). Helpful diagnostic guidelines were drawn up from the results of the cytogenetic analysis and clinical study of 44 different marker chromosomes, published in 1985 (Buckton et al. 1985). Fluorescence in situ hybridization (FISH) with chromosome-specific probes has made identification feasible (Callen et al. 1991, Schwartz et al. 1991), but because of the variety of marker chromosomes differing in morphology, identity and possible significance, substantially more observations are needed to confirm previous results and the cases reported here.

.

84

March,

Material, methods, and cases Cytogenetics

Chromosome spreads were prepared from PHAactivated lymphocytes and staining was performed by a variety of cytogenetic techniques (GTG, CBG, DA-DAPI, Ag-NOR) by standard procedures. In case 6, the karyotype was studied from amniocytes and fetal tissues after abortion. The sizes of the marker chromosomes are compared to the length of the short arm of a no. 18 after GTG banding. Probes and FISH

Phage libraries of the human chromosomes 1-22,

X and Y were obtained from the American type culture collection. Amplification, purification and extraction of phage-DNA were carried out following the protocols from Sambrook et al. (1989). DNA was labelled with Biotin-1 1-dUTP (Sigma) using a nick-translation kit (BRL) following the supplier’s instruction. Alphoid and sat111 DNA probes specific for centromeres of no. 3,7, 11, 13/ 21, 15, 18 and X were purchased from Oncor Inc. The probe 14/22 (EAN 02) was kindly provided by R. Fahsold (Erlangen). The alphoid probe 15 (pTRA-20) was a gift from K. H. A. Choo (Choo et al. 1990). In situ hybridization was performed after the protocol by Lichter et al. (1988) with minor modifications.

Marker chromosomes identified by FISH Chromosome preparations were counterstained with DAPI and propidium iodide, and mounted with antifade solution. The slides were examined by a fluorescence epiillumination system (Leitz), and photographs were taken with Agfachrome 1000 RS color slide film. Case reports (Table 1)

1. S 88 47,XX +mar (15). The marker chromosome was found in amniotic fluid cells of the first pregnancy of a healthy 36-year-old female. The normal unrelated husband was 43 years of age. The female child, born after the pregnancy was continued, has been normally developing and did not exhibit dysmorphic features when examined at age 2 1I 2 years.

2. N N 891218 46,XY/47,XY+idic(I5). First child of healthy, unrelated parents. At his birth paternal age was 32, and maternal age 27 years. The uneventful pregnancy was continued to term, when cesarean section was carried out. Weight was 3570 g, length was 50 cm, and head circumference (HC) was said to be 38 cm. The patient was referred because of tetralogy of Fallot and various dysmorphic signs including macrocephaly, hypertelorism, low-set ears, long philtrum, thin mucosal upper lip, upturned nose, median dimple of the nasal bridge, and short neck. Moreover, severe congenital hypothyroidism was noted. Correction by Blalock-Taussig shunt was not permanently successful. At age 2.4 years psychomotor development was retarded. 3. JB 891214 47,XY,+i(18p). The third child of healthy, unrelated parents. At his birth paternal age was 47 years, and maternal age 42 years. Pregnancy and delivery at term were uneventful. His weight was 3120 g, length 51 cm,and HC 33 cm. Apgar score was 91 10110. His opisthotonic posture was related to intrauterine malposition. Referral

was because of failure to suck and cyanotic fits. Examination showed connatal pneumonia. Cardiovascular abnormalities were ruled out by sonography. NMR of the brain in the 3rd week did not reveal morphologic anomalies but suggested immaturity of the brain stem. The fundus of the eye was normal for age. Biochemical and immunological findings were normal. Microcephaly, mild facial dysmorphism, such as deep nasal bridge and low-set ears, and considerable psychomotor retardation were noted. He suffered mainly from frequent gastro-esophageal regurgitation at age 2 years. 4. MB 730926 46,XY/47,XX+mar(I8).The propositus is the only child of healthy, unrelated, parents. The father was known to have unilateral renal duplication. At the birth of the propositus, paternal age was 31, and maternal age 30 years. The uneventful pregnancy was terminated by cesarean section. Birth weight was 2600 g, and length 51 cm. He had imperforate anus with a perineal fistula, dysplastic left kidney with ipsilateral megaureter and vesicoureteral reflux. Furthermore, VSD and mild valvular pulmonic stenosis, right cleft lip and palate, microtia without appendages, and conductive hearing loss due to stapedial fixation were noted. Echography of the brain at the age of 8 months showed generalized dilatation of the ventricles. Ophthalmological findings were normal. Mental milestones were moderately retarded. At the age of 16 years, height was 180 cm.There was craniofacial dysmorphism, and the thumbs were long and slender.

5. A E 890520 46,XX/47,XX,+mar(3). The patient is the second child of healthy, unrelated parents. There had been one miscarriage. Paternal age was 45, and maternal age 39 years. The pregnancy was uneventful. Pre-term sonography suggested an abnormality of the kidney. After birth, multicystic

Table 1. Summary of cytogenetic findings and FISH Case

Karyotype

1 2 3 4 5 6 7 8 9 10

-

Phenotype

Karyotype of parents

normal tetralogy of Fallot, dysmorphic features, mild MR cardiovascular abnorm.. dysmorphic features, MR imperforate anus, dysplastic kidney, VSD. cleft lip and palate, microtia, mild MR dysplastic kidney normal dysmorphic features, carious teeth, MR trisomy 21 mosaicism antimongolism dysmorphc features, cryptorchidism, hydrocephalus, severe MR

father 47,XY,+rnar(l5) normal normal normal normal normal normal normal mother 46,XX (68%). 47,XX.+idc(22) (32%) normal

85

Rauch et al. dysplasia of a nonfunctional left kidney was discovered. Birthweight at the 37th week of pregnancy was 2030 g. She was referred at the age of 7 months because of meningitis. Body measurements at this time and at the age of 11 months were at the 10th percentile. Her motor and mental milestones have been considered normal. No dysmorphic features were noted. 6. M A 8389 46,XY/47,XZ+mar(3).The additional marker chromosome was discovered in amniotic fluid cells after amniocentesis during the 4th pregnancy of a healthy 36-year-old woman. Three previous pregnancies were spontaneously aborted. Because of uncertain prognosis the pregnancy was aborted. The male fetus was normal for 18 weeks of gestation and did not exhibit malformations or dysmorphic features. 7. CE 861106 46,XX/47,XX, +mar(ll). She is the second of three children. At her birth, paternal age was 25 and maternal age 24 years. One previous pregnancy was aborted in the 1 lth week. Delivery by cesarean section in the 30th week subsequent to amniotic rupture had been preceded by vaginal discharges. Weight was 1250 g, length 40 cm, and HC 27.5 cm (normal for gestational age). She suffered from pulmonary asphyxia, probably due to hypoplasia of the epiglottis. Intracerebral haemorrhage with mild dilatation of the left lateral ventricle was suggested. Malformations of the cardiovascular and urogenital systems were ruled out. Minor facial dysmorphy, such as micrognathia and low-set ears, was noted. Motor and mental development have been retarded. At the age of 4; years, body measurements were at the 3rd percentile. There was minor hypertelorism (+ 1.5 SD),epicanthus, broad nasal bridge, poorly shaped alae nasi, long philtrum and thin vermilion border to the lips. The teeth were all carious and broken, and only one permanent lower incisor had erupted.

8. H H 46,XY/47,XX++ar(21). The propositus is the first child of normal, unrelated parents. At his birth paternal age was 32 years, and maternal age 35 years. “Mongol” features were noted from infancy, such as flat facies, brachycephaly, speckled iris, muscular hypotcnia, and minor motor and mental retardation. At this time (1972), an additional minute chromosome was found in lymphocytes, and partial trisomy 21 was suggested. Childhood and adolescence were uneventful. He finished primary school without difficulty and has been employed until now as a skilled worker. His personality appeared rather immature and unstable. 86

Intelligence was average, but no specific testing was carried out. At the age of 22 years, body measurements were within normal range. Features of Down’s syndrome present were straight hair, Brushfield spots of the iris, and furrowed tongue. Dermatoglyphics were “at the borderline of trisomy 21 mosacism”. 9. JD 910722 46,XX.r(21)/45,XX,-21/47, XX,r(2I), +mar(2l).The patient is the only child of healthy, unrelated parents. Paternal age at birth was 22, and maternal age 20 years. The pregnancy and delivery were uneventful. Weight was 3080 g, and length 48 cm. Apgar score was 41819. He was referred because of asphyxia, thought to be related to laryngeal abnormality and facial dysmorphism: low forehead, antimongoloid slant of palpebral fissures, narrow lips, low-set ears, microretrognathia, but also large hands and irregularly inserted toes. 10. DS 850520 46,XY/47,XZ+mar(X). The patient is the elder of two children. The unrelated parents are healthy. Paternal age was 29, and maternal age 28 years. The pregnancy was uneventful. Delivery was prolonged and terminated by vacuum extraction. Birth weight was 3450 g, length 55 cm, and HC 36 cm. Apgar score was 8/9/10. At the age of 2 months inguinal hernias and cryptorchidism were surgically corrected. By echography of the brain, mild enlargement of the ventricles was visualized. He was referred because of adducted low inserted thumbs, dysplastic ears, hemangioma of the upper eyelid, alae nasi and philtrum. His motor and mental development have been severely retarded.

Results and comments Uable 21

Cytogenetic findings displayed an unexpected diversity (Table 1). In all but two cases (nos. 2 and 3), the marker did not show specific G-banding features. Chromosome 15

The origin of the markers in cases 1 and 2 had been shown previously by NOR and DA/DAPI staining. In case 2 the marker was consistent with idic( 15). In case 1 the marker, though metacentric after labelling with the alphoid probe 15, was asymmetric with regard to labelling with satIII. According to Ag-NOR positive banding, satellites were present on the unlabelled arm. The same marker was present in the father but no signal was obtained on one no. 15 when probed with sat111 DNA (Fig. la); a weak signal was noted after labelling with

Marker chromosomes identified by FISH Table 2. Summary of clinical and cytogenetic data

Marker 1 2 3 4 5 6

7 8 9 10

15 Miil5) Yl8p) 18 3 3 11 21 21 X

Size' (#lap)

Mitoses

+mar (%)

CBG

A* NOR

312

100

+

+

2

90

+I+

+I+

2 112 1 1 1 2/3 1 1I 4

100 64 56 80 50 50 20 70

-

-

+ +

+ +

+ +

(+I

-

DAl DAPl

Library prod

(+)

LA15NS02

+

+I+

+

-

-

-

-

Centromeric probes

lA18NSO4 + lA18NS04 + iA03NSO2 + LL21NS02 + U21NS02 + UOXNSOl +

Dl 521 Dl521 D1821 Dl821 D3Z1 D321 Dl121 D2121ID1321 D2121lD1321 DXZl

+ ++

+I+

-

+

+ + + +

+

' Size with reference to the length of 18 p (GEL

' Chmsoms specific libraries.

' Alphoid and satellite 111 (01521) DNA probes

-

(+)

+ ++ +I+

negative. weakly positive. posithrs, one signal positive, larger signal than normal positiw, two separate bands or bisateliied (NOR).

alphoid DNA. Marker chromosomes derived from no. 15 were analysed by Steinbach et al. (1983) and other authors. From a clinical standpoint these cases are obviously heterogeneous, and molecular studies will be needed to reveal the correlation between cytogenetic and phenotypic manifestations (Plattner et a]. 1991). The organisation of idic( 15) with regard to Prader-Willi-Labhart syndrome is particularly interesting (Smith et al. 1989). The general rule that familial cases with a normal phenotype are genetically inert while de novo cases may be unbalanced holds true, but exceptions are expected.

ring chromosome derived from no. 3 was shown in a female with nonspecific clinical features (Callen et al. 1991). This marker chromosome, observed both in amniocytes and in fetal tissues, is likely to be genetically inert because the aborted fetus (case 6) appeared normal. Moreover, in case 5 (Fig. 2c) the association with cystic dysplasia of one kidney in an otherwise normal child may be random.

Chromosome 18

Chromosome 11

In case 3, i(18p) was suggested after G-banding. This patient shares facial dysmorphic features with the i(18p) phenotype as analysed from 25 (Brondum-NieIsen et al. 1978), 18 (Rivera et al. 1984), and 9 (Callen et al. 1990a) published cases. It is noteworthy that gross abnormalities are lacking. Pre-chromosome-banding literature contains many such observations, from which the syndrome of the metacentric chromosome was deduced (Abbo & Zellweger 1970). FISH was first used for identification in i(l8p) by Callen et al. (1990b) and Blennow & Brondum-Nielsen (1991). In patient 4, who had first been studied 14 years before, the cytogenetic diagnosis of a marker no. 18 was unexpected because the malformations fitted the clinical picture of cat-eye syndrome. It is noteworthy that this marker was CBG but also negative for the alphoid probe 18. Since the marker is mitotically stable, it should contain a kinetochore (Fig. 2a, 2b).

In patient 7 the marker derived from no. 11 (Fig. 2d) may be causally related to multiple dysmorphic features. However, there is little resemblance with the unique patient in which an acrocentric marker was shown by increased LDH A to be partial trisomy l l p (Rethort et al. 1980).

Chromosome 3

A marker chromosome derived from no. 3 has not been reported before to our knowledge. A small

Chromosome 21

Markers having shown to be NOR positive but DA/DAPI negative were narrowed down using the alphoid probes 13/21 and 14/22 first, and finally specified by genomic libraries of no. 21 and no. 22. These strong signals differ significantly from weak signals caused by cross-hybridization with other acrocentric chromosomes (Fig. lc, Id). Patient 8 has been followed for more than 20 years. Down's syndrome had been suggested from early childhood. 87

Rauch et al.

Fig. 1. (markers derived from acrocentric chromosomes). fa. Centromeric probe of no. 15 (sat111 DNA) labelling the marker and one chromosome 15 in the father (case 1). The arrow points to the unlabelled no. 15 previously identified by DAPI banding. fb. idic (22) (arrow) in the mother of case 9 after hybridization with the alphoid 14/22 DNA probe. - Marker chromosome 21 (case 8) after labelling with alphoid 13/21 DNA probe. The arrows point to the marker and one chromosome 21 exhibiting alphoid DNA polymorphism (Ic). Chromosomes 21 and the marker are equally labelled with the DNA library 21 (Id).

In case 9 the phenotype shares some features with so-called antimongolism (Richer et al. 1981, Crusi & Engel 1986). Various cell lines may arise due to the mitotic instability of this ring and/or sister chromatid exchange with inverted polarity. An additional marker was identified by a 21 library probe. In the mother an additional marker chromosome was found in 16/50 metaphases. Unexpectedly, it was shown to be an idic (22) (Fig. 1b). The apparent coincidence of two different unrelated markers was reported by Heppell-Parton & Waters (1991), who discovered that in a familial case of rob( 14q21q) an extra microchromosome was constituted of parts of no. 15, and hence was obviously unrelated and separately transmitted. X chromosome

In case 10 the origin of the marker was unexpected and there may be no correlation with the phenotype. Fragments of the X have been found in females who only exhibited features of Turner’s syn88

drome (Cooper et al. 1991, Lin et al. 1990). It seems rather unlikely that the marker chromosome is the cause of the MA/MR syndrome in this male because of the relatively benign phenotype of XXY males. Discussion

Although numerous observations of supernumerary chromosomes with various cytogenetic morphologies have been published over the past 30 years, their clinical significance in individual cases has been a major problem and has led to various speculations on karyotype-phenotype correlation. Thus the intriguing finding of acrocentric G-like chromosomes in nonmongoloid individuals was discussed for a while (Zellweger et al. 1962) and a “syndrome of the metacentric chromosome” (Abbo & Zellweger 1970) was proposed. Small supernumerary ring chromosomes of different sizes and origins were shown to produce some common although nonspecific clinical features (Kosztolanyi

Marker chromosomes identified by FISH

Fig. 2. (markers derived from nonacrorrntric chromosomes). 2u and 26. Lack of signal on the marker in case 4 labelled with alphoid DNA probe 18 (24, but positive signal with the DNA library of no. 18 (2b). 2c. Centromeric probe labelling the marker and both chromosomes no. 3 in case 5. 2d. Ccntromeric probe labelling the marker and both chromosomes no. 1 1 in case 7.

1987). When nonfluorescent minute marker chromosomes were discovered in intersex individuals with one or even two X chromosomes, they were considered likely to be deleted Y chromosomes. Till now, small supernumerary marker chromosomes have been classified using morphological variants, such as satellites or centricity, and staining peculiarities by CBG- or DA/DAPI-banding (Buckton et al. 1985). Large markers, including both acrocentric and metacentric chromosomes, even after GTG and CBG banding, are often not identified with certainty, so that any correlation with clinical features remained speculative. A marker containing NORs was the first to be recognized by in situ hybridization (ISH) with rDNA (Johnson et al. 1974), and in 1985 a marker was identified as i(l8p) by ISH, with a radioactive probe (Mattei et al. 1985). Because of their diagnostic importance, Y fragments have been identified with Y-specific probes (Crolla et al. 1989, Jauch et aI. 1990, Lin et al. 1990). Since the identification of unclassifiable markers has become feasible using specific non-radioactive

probes in situ, it has been shown that centromeric fragments may derive from centromeric regions of chromosomes 1, 9, and 16 (Callen et al. 1990a, Raimondi et al. 1991) and 13 and 15 (Bartsch & Schwinger 1991). Our study confirms the findings of Callen et al. (1991) and Schwartz et al. (1991) and emphasises that small markers may also be derived from other chromosomes such as no. 3, 11, 18, 21, 22, and X as well. Their significance in individual cases is still difficult to clarify and it is impossible to know yet which features are caused by particular aberrations and which are nonspecific findings. The search for the origin of the marker may be time-consuming whenever morphology and conventional staining do not point to the candidate. Alphoid probes may be preferred for identification unless the marker is C-negative. Quantitative polymorphism of alphoid and sat111 DNA have to be taken into account. Minute markers are commonly tested with many probes. This procedure can be simplified when centromeric probes are used under less stringent conditions because with cross-hybridization more than

84

Rauch et al. one known chromosome would be selected, e.g. the X-specific alphoid probe labels centromeres of no. 1 1 and 17 as well. Acknowledgements The authors are grateful to numerous colleagues who provided them with clinical data. The expert technical assistance of M n . S. Reichardt, Mrs. I. Janker and Mn. R. Linsenmeyer is acknowledged. Dermatoglyphics in patient 8 were examined by Prof. A. Rodewald, Hamburg.

Rderencas Abbo G, Zellweger H. The syndrome of the metacentric microchromosomes. Heiv Paediatr Acta 1970 25: 83-94. Bartsch 0, Schwinger E. A simplified protocol for fluorescence in situ hybridization with repetitive DNA probes and its use in clinical cytogenetics. Clin Genet 1991: 40:47-56. Benn PA, Hsu LYE Incidence and significance of supcrnumerary marker chromosomes in prenatal diagnosis. Am J Hum Genet 1984 36: 1092-1102. Blennow E, Brbndum-Nielsen K. Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18pwith probe L1.84. Clin Genet 1991: 3 9 429433. Brbndum-Nielsen K, Dyggve H, Friedrich U, Hobolth N, Lyngbye T, Mikkelsen M. Small metacentric nonsatellited extra chromosome. Hum Genet 1978: 44.59-69. Buckton KE, ORiordan ML, Ratcliffe S, Slight J, Mitchell M. Mcbeath S. A G band study of chromosomes in liveborn infants. Ann Hum Genet 1980 43: 227-239. Buckton KE, Spowart G, Newton MS. Evans HJ. Forty four probands with an additional “marker” chromosome. Hum Genet 1985: 69: 353-370. Callen DF, Eyre HJ, Ringenbergs ML, Freemantle CJ, Woodroffe P, Haan EA. Chromosomal origin of small ring marker chromosomes in man: characterization by molecular genetics. Am J Hum Genet 1991: 48: 769-782. Callen DF, Freemantle CJ, Ringenbergs ML, Baker E, Eyre HJ, Romain D, Haan EA. The isochromosome 18p syndrome: confirmation of cytogenetic diagnosis in nine cases by in situ hybridization. Am J Hum Genet 1990a: 47: 493-498. Callen DF, Ringenbergs ML, Fowler JCS, Freemantle CJ, Haan EA. Small marker chromosomes in man: origin from pericentric heterochromatin of chromosomes 1, 9, and 16. J Med Genet 1990b: 27: 155-159. Choo KH, Earle E, Vissel B, Filby RG. Identification of two distinct subfamilies of alpha satellite DNA that are highly specific for human chromosome 15. Genomics 1990: 7: 143-1 5 I. Cooper C, Crolla JA, Laister C, Johnston DI, Cooke P. An investigation of ring and dicentric chromosomes found in three Turner’s syndrome patients using DNA analysis and in situ hybridisation with X and Y chromosome specific probes. J Med Genet 1991: 28: 6-9. Crolla JA, Smith M, Docherty 2.Identification and characterisation of a small marker chromosome using non-isotopic in situ hybridisation with X and Y speciiic probes. J Med Genet 1989: 26: 192-197. Crusi A, Engle E. Diagnostic prenatal de trois cas de chromosome G en anneau: un 21 et deux 22, dont un de novo. Ann Genet 1986: 29: 253-260. Dahoun-Hadorn S, Delozier-Blanchet C. Reflections on small supernumerary (marker) chromosomes: could imprinting and isodisomy play a role in the phenotypic expression of hyperdiploidy? Ann Genet 1990: 33: 241-242.

90

Heppell-Parton AC, Waters JJ. Robertsonian translocation and an extra microchromosome: independent origin identified by in situ hybridization. Clin Genet 1991: 3 9 93-96. Jauch A, Daumer C. Lichter P, Murken J. Schrocder-Kurth T, Cremer T. Chromosomal in situ suppression hybridization of human gonosomes and autosomes and its use in clinical cytogenetics. Hum Genet 1990.85: 141-150. Johnson LD, Hams RC. Henderson AS. Ribosomal DNA sites in a metacentric chromosome fragment. Humangenetik 1974: 21: 217-219. Kosztolanyi G. Does a “ring syndrome” exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 1987: 75: 174-179. Lichter P,Crcmer T.Borden J, Manuelidis L. Ward DC. Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet 1988: 80: 224234. Lin CC, Meyne J, Sasi R, Bowen P, Unger T, Tainaka T,Hadro TA. Hoo JJ. Determining the origins and the structural aberrations of small marker chromosomes in two cases of 45,X/ 46,X, +mar by use of chromosome specific DNA probes. Am J Med Genet 1990. 37: 71-78. Martin RH, Hildebrand KA,Yamamoto J, Peterson D, Rademarker AW, Taylor P, Lin CC. The meiotic segregation of human sperm chromosomes in two men with accessory marker chromosomes. Am J Med Genet 1986 25: 381388. Mattei MG, Philip N, Passage E. Moisan JP, Mandel JL, Mattei JF. DNA probe localization at 18pl13 band by in situ hybridization and identification of a small Supernumerary chromosome. Hum Genet 1985 6 9 268-271. Plattner R, H e e m NA, Patil SR, Howard-Pccbles PN. Palmer CG. Characterization of Seven DAIDAPI-positive bisatellitcd marker chromosomes by in situ hybridmtion. Hum Genet 1991: 87: 290-296. Raimondi E, Ferretti L, Young BD, Sgaramella V, de Carli L. The origin of a morphologically unidentifiable human supernumerary minichromosomc traced through sorting, molecular cloning, and in situ hybridization. J Med Genet 1991: 28: 92-96. RethorL M-0, Junien C, Aurias A, Couturier J. Dutrillaux B, Kaplan JC, Lejeune J. Augmentation de la LDH A et trisomie 1 I p partielle. Ann Genet 1980: 23: 35-39. Richer C-L, Fitch N, Sitahal S, Murer-Orlando M. Jean P. Analysis of banding patterns in a case of ring chromosome 21. Am J Med Genet 1981: 10: 323-331. Rivera H, Moller M, Hernandez A, Enriquez-Guerra MA, Arreola R, Cantu JM. Tetrasomy 18p: a distinctive syndrome. Ann Genet 1984 27: 187-189. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning. A laboratory manual. New York: Cold Spring Harbor Lab Press, 1989. Schwartz S,Wolff DJ, Zackowski JL. Identification of chromosomal markers and rearrangements utilizing fluorescence hybridization. Cytogenet Cell Genet 1991: 56: 224. Smith A, Den Dulk G, Lipson A, Suter M. Classical PraderWilli syndrome with trisomy 15@ter-q12)plus de novo variant 15pll. Ann Genet 1989: 32: 39-42. Steinbach P, Djalali M, Hansmann I, Kattner E, Meisel-Stosiek M,Probeck H-D, Schmidt A, Wolf M. The genetic significance of accessory bisatellited marker chromosomes. Hum Genet 1983: 65: 155-164. Warburton D. Outcome of cases of de novo structural rearrangements diagnosed at amniocentesis. Prenat Diagn 1984 4: 69-70. Zellweger H, Mikamo K, Hokkaido. Abbo G.Two cases of non-mongoloid trisomy G. Ann Paediatr 1962: 199: 613624.

A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH).

In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for parti...
720KB Sizes 0 Downloads 0 Views