Delineation of supernumerary marker chromosomes in 38 patients

Viersbach, Renate; Engels, Hartmut; Gamerdinger, Ulrike; Hansmann, M.

doi:10.1002/(sici)1096-8628(19980401)76:4<351::aid-ajmg12>3.0.co;2-n

Cited by 60 publications

(31 citation statements)

References 35 publications

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“…Based on the comparison of clinical features of sSMC(18) carriers described earlier, we propose that tri-or tetrasomy of pericentromeric region of chromosome 18 results in tapering of fingers and motor developmental delay -features found also in patient MK (Viersbach et al 1998;Baumer et al 2002;Starke et al 2003;Guanciali-Franci et al 2004;Timur et al 2004;Bartsch et al 2005).…”

Section: Discussionmentioning

confidence: 75%

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Pietrzak¹,

Mrasek

Obersztyn³

et al. 2007

J Appl Genet

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Small supernumerary marker chromosomes (sSMCs) are a morphologically heterogeneous group of additional structurally abnormal chromosomes that cannot be identified unambiguously by conventional banding techniques alone. Molecular cytogenetic methods enable detailed characterization of sSMCs; however, in many cases interpretation of their clinical significance is problematic. The aim of our study was to characterize precisely sSMCs identified in three patients with dysmorphic features, psychomotor retardation and multiple congenital anomalies. We also attempted to correlate the patients' genotypes with phenotypes by inclusion of data from the literature. The sSMCs were initially detected by G-banding analysis in peripheral blood lymphocytes in these patients and were subsequently characterized using multicolor fluorescence in situ hybridization (M-FISH), (sub)centromere-specific multicolor FISH (cenM-FISH, subcenM-FISH), and multicolor banding (MCB) techniques. Additionally, the sSMCs in two patients were also studied by hybridization to whole-genome bacterial artificial chromosome (BAC) arrays (array-CGH) to map the breakpoints on a single BAC clone level. In all three patients, the chromosome origin, structure, and euchromatin content of the sSMCs were determined. In patient RS, only a neocentric r(2)(q35q36) was identified. It is a second neocentric sSMC(2) in the literature and the first marker chromosome derived from the terminal part of 2q. In the other two patients, two sSMCs were found, as M-FISH detected additional sSMCs that could not be characterized in G-banding analysis. In patient MK, each of four cell lines contained der(4)(:p11.1-->q12:) accompanied by a sSMC(18): r(18)(:p11.2-->q11.1::p11.2-->q11.1:), inv dup(18)(:p11.1-->q11.1::q11.1-->p11.1:), or der(18) (:p11.2-->q11.1::q11.1-->p11.1:). In patient NP, with clinical features of trisomy 8p, three sSMCs were characterized: r(8)(:p12-->q11.1::q11.1-->p21:) der(8) (:p11.22-->q11.1::q11.1-->p21::p21-->p11.22:) and der(21)(:p11.1-->q21.3:). The BAC array results confirmed the molecular cytogenetic results and refined the breakpoints to the single BAC clone resolution. However, the complex mosaic structure of the marker chromosomes derived from chromosomes 8 and 18 could only be identified by molecular cytogenetic methods. This study confirms the usefulness of multicolor FISH combined with whole-genome arrays for comprehensive analyses of marker chromosomes.

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Section: Discussionmentioning

confidence: 75%

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Pietrzak¹,

Mrasek

Obersztyn³

et al. 2007

J Appl Genet

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“…It has been shown that de novo marker chromosomes are associated with an increased risk of mental retardation and/ or physical anomalies (1,5,11). Pre-natally ascertained cases of sSMC that have arisen de novo are particularly difficult to connect clinically to a phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…The large variety of sSMCs, as well as the limitations in their cytogenetic identification, have presented a diagnostic problem in their interpretation. In general, the risk for an abnormal phenotype is approximately 13%, varying from 7% when de novo sSMCs derived from chromosomes 13, 14, 21 and 22 are encountered, to 28% for non-acrocentric (5). Studies of the cytogenetic and phenotypic effects of sSMCs gained a fresh impetus when fluorescence in situ hybridization (FISH) was utilized to identify their chromosomal origin (6).…”

Section: Introductionmentioning

confidence: 99%

Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization

Manolakos¹,

Kefalas²,

Neroutsou³

et al. 2010

Mol Med Rep

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Abstract. Small supernumerary marker chromosomes (sSMCs) cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques. Until recently, the large variety of marker chromosomes, as well as the limitations in their identification, have presented a diagnostic problem. In order to determine the origin of sSMCs, we used a variety of fluorescence in situ hybridization (FISH) methods, including centromere-specific multicolor FISH, acrocentric specific multicolor FISH, subcentromere-specific multicolor FISH and multicolor FISH with whole chromosome paint probes. Moreover, uniparental disomy testing was in all cases attempted. From a total of 28,000 pre-natal samples from four diagnostic genetics laboratories in Greece, 23 (0.082%) supernumerary marker chromosomes were detected. The mean maternal age was 36.2 years (range 27-43) and the mean gestational age at which amniocentesis was performed was 18.5 weeks (range 16-23). Eighteen markers were de novo and 5 markers were inherited. Molecular cytogenetic methods were applied to determine the chromosomal origin and composition of the sSMC. In total, 17 markers were derived from acrocentric chromosomes (14, 15, 21 and 22) and 6 markers were non-acrocentric, derived from chromosomes 9, 16, 18, 20 and Y. Uniparental disomy was not detected in any of the cases studied. With regard to pregnancy outcome, 13 pregnancies resulted in normal healthy neonates, while 10 pregnancies were terminated due to ultrasound abnormalities. A total of 23 marker chromosomes from 28,000 pre-natal samples (0.082%) were identified. Molecular cytogenetic techniques provided valuable information on the chromosomal origin and composition of all the sSMCs. Especially in cases with normal ultrasound, the FISH results rendered genetic counseling possible in a category of cases previously considered a diagnostic problem. Abnormal outcome was observed in 10 cases (43,5%), 7 of which showed abnormal ultrasound findings. New technologies, such as array-comparative genomic hybridization, should be used in future genotype-phenotype correlation studies, although the high mosaicism rate poses a problem. IntroductionSmall supernumerary marker chromosomes (sSMcs) are structurally abnormal chromosomes, equal in size or smaller than chromosome 20, which cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques (1). These chromosomes are detected in 0.04% of newborn children, whereas in developmentally retarded patients the rate is 0.22% (1-3). sSMCs are also present in 0.08% of unselected pre-natal cases and in 0.20% of pre-natal cases with ultrasound abnormalities (2). The large variety of sSMCs, as well as the limitations in their cytogenetic identification, have presented a diagnostic problem in their interpretation. In general, the risk for an abnormal phenotype is approximately 13%, varying from 7% when de novo sSMCs derived from chromosomes 13, 14, 21 and 22 are encountered, to 28% for non-acrocentric

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“…The girl reported by Silahtaroglu et al (1995) was mentally retarded and had impaired speech and moderate dysmorphic facial features. A low-level mosaicism with a small extra ring X chromosome was found in a phenotypically normal girl (case 37, Viersbach et al 1998). Neither of these patients have features consistent with HI, but neither XIST status nor X-inactivation studies were carried out.…”

Section: Discussionmentioning

confidence: 94%

Pigmentary mosaicism in hypomelanosis of Ito

Fritz

Küster

Ørstavik³

et al. 1998

Human Genetics

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We report on a female with mental and motor retardation, facial dysmorphism, abnormal pigmentation reminiscent to hypomelanosis of Ito (HI), and karyotypic mosaicism involving a small supernumerary marker chromosome. The marker chromosome was defined by fluorescence in situ hybridisation (FISH) as a ring X chromosome with breakpoints in the juxtacentromeric region. FISH analysis showed that the ring does not include the XIST locus at the X-inactivation centre and, therefore, may not be subject to X inactivation. X-inactivation studies with the HUMARA (human androgen receptor) and FMR1 assay showed a skewed X-inactivation pattern (85:15) with preferential inactivation of the paternal X chromosome. These results are discussed with respect to the role of functional disomy of Xp in the pathogenesis of HI.

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Delineation of supernumerary marker chromosomes in 38 patients

Cited by 60 publications

References 35 publications

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization

Pigmentary mosaicism in hypomelanosis of Ito

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