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Molecular characterization of a rare analphoid supernumerary marker chromosome derived from 7q35???qter: a case report.

ABSTRACT: BACKGROUND:Analphoid supernumerary marker chromosomes (aSMC) constitute one of the smallest groups of SMC, and are characterized by a centromeric constriction but no detectable alpha-satellite DNA. These marker chromosomes cannot be properly identified by conventional banding techniques alone, and molecular cytogenetic methods are necessary for a detailed characterization. Analphoid SMC derived from chromosome 7 are extremely rare, with only five cases reported so far. CASE PRESENTATION:In this work we report an aSMC involving the terminal long arm of chromosome 7 in a 10-year-old boy with multiple dysmorphic features and severe development delay. Cytogenetic analysis revealed a mosaic karyotype with the presence of an extra SMC, de novo, in 20% of lymphocytes and 73% of fibroblast cells. Next, we performed FISH analysis with multiple DNA probes and cCGH analysis. This identified the origin of the SMC as an analphoid marker resulting of invdup rearrangement of 7q35-qter region. Affimetrix CytoScan HD array analysis redefined the aSMC as a 15.42 Mb gain at 7q35-q36.3 (minimum tetraplicated region-chr7: 143,594,973-159,119,707; GRCh37/hg19) of maternal origin that encloses 67 OMIM genes, 16 of which associated to disease. Uniparental disomy of chromosome 7 (UPD 7) has been excluded. CONCLUSIONS:We report the first patient with an aSMC(7) derived from the terminal 7q region who has been molecularly and clinically full characterized. The use of SNParray in the characterization of SMC reveals to be a powerful tool, giving information not only about copy number variation but also about loss-of-heterozygosity and parental origin. We conclude that an integrated genome-wide copy number variation analysis, if possible associated to FISH and gene expression studies, could facilitate in the future the difficult task of establishing accurate genotype-phenotype correlations and help to improve genetic counselling.

SUBMITTER: Marques B

PROVIDER: S-EPMC5123314 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Molecular characterization of a rare analphoid supernumerary marker chromosome derived from 7q35 → qter: a case report.

Marques Bárbara B Ferreira Cristina C Brito Filomena F Pedro Sónia S Alves Cristina C Lourenço Teresa T Amorim Marta M Correia Hildeberto H

Molecular cytogenetics 20161125

<h4>Background</h4>Analphoid supernumerary marker chromosomes (aSMC) constitute one of the smallest groups of SMC, and are characterized by a centromeric constriction but no detectable alpha-satellite DNA. These marker chromosomes cannot be properly identified by conventional banding techniques alone, and molecular cytogenetic methods are necessary for a detailed characterization. Analphoid SMC derived from chromosome 7 are extremely rare, with only five cases reported so far.<h4>Case presentati ...[more]

PMID: 27924152

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Project description:This study aimed to report a rare case of intermittent azoospermia and ring-like small supernumerary marker chromosomes (sSMCs). An infertile man was diagnosed with azoospermia presenting a normal male phenotype with complete masculinization. Karyotyping and polymerase chain reaction (PCR) were used to detect 16 sequence-tagged sites on the AZF subregions of the Y chromosome, and 115 candidate genes were screened for mutations. Mutations included single nucleotide variations, insertions, and deletions. Metaphase chromosomes were studied by standard trypsin-Giemsa banding; fluorescent in situ hybridization and PCR were performed to analyze specific Y chromosome regions; gene mutations were detected. Chromosomal analysis detected 117 metaphase cells; a mosaicism with marker 1 and marker 2 sSMCs in 2 metaphase cells (47, X, +mar1x2 karyotype), a mosaicism with marker 2 sSMCs in 14 metaphase cells (46, X, +mar2 karyotype), and a mosaicism with marker 1 sSMCs in 76 metaphase cells (46, X, +mar1 karyotype), coexisting with a 45,X cell line in the remaining 25 metaphase cells. PCR analysis showed the sY160 heterochromosome on the AZFc subregion was absent. Next-generation sequencing identified an asthenozoospermia-specific mutation in GAPDHS (rs2293681), and Sanger sequencing verified this mutation. This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility. A mosaic 46, X, +mar1[76]/45, X[25]/46, X, +mar2[14]/47, X, +mar1x2[2] karyotype could be the main explanation for the azoospermia/severe oligospermia, while the likely pathogenic GAPDHS intron mutation may contribute to the symptom of immotile sperms detected in the semen analysis.

Dataset Information

Molecular characterization of a rare analphoid supernumerary marker chromosome derived from 7q35???qter: a case report.

Publications

Molecular characterization of a rare analphoid supernumerary marker chromosome derived from 7q35 → qter: a case report.

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