Reflection of a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotyping analysis / 中华医学遗传学杂志

Objective@#To emphasize the clinical significance of copy number variations (CNVs) detection by describing a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis.@*Methods@#A girl with obesity and short stature was diagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis. Considering the discrepancy of her karyotype with her phenotype, genomic CNVs was detected by next-generation sequencing and the result was verified by quantitative PCR (qPCR).@*Results@#A microduplication of 16p11.2: 29 642 339-29 775 631 (133.292 kb) was detected. qPCR assay for QPRT and SPN located in the duplicated region confirmed the finding of CNVs assay. Meanwhile, her parents did not present similar duplication in 16p11.2.@*Conclusion@#The 16p11.2 microduplication was a novel genomic structural variation in the girl, though it may not be associated with her clinical manifestations. Chromosomal microarray or next-generation sequencing-based CNVs detection can accurately determine the origin of small supernumerary marker chromosome and reduce the chance of misdiagnosis.

Small supernumerary marker chromosome and chromosome 18p abnormalities / 中华实用儿科临床杂志

Humans typically have 22 pairs of autosomal chromosomes in cells,and a pair of sex chromosomes.Some individuals have an extra,autosomal chromosome called a small supernumerary marker chromosome (sSMC).sSMC is a structurally abnormal chromosome fragment.The fragments are too small and no-specific banding pattern to be identified by conventional banding cytogenetic analysis.Array-based comparative genomic hybridization (aCGH),fluorescence in situ hybridization (FISH) or other molecular biological methods are necessary for the diagnosis.This article summarized the karyotype,pathogenesis,and the clinical manifestations of the sSMC-related chromosome 18p abnormalities.The patients with sSMC usually presented with abnormal chromosome syndrome.Some syndromes are relative common,such as Pallister-Killian syndrome,isochromosome 18p syndrome,Cat eye syndromes or Emanuel syndrome.sSMC is considered to be the frequent cause of mental retardation.The patients have no specific symptoms.With the progress of molecular cytogenetics,more sSMC has been identified.Genetic counseling and prenatal diagnosis are important to prevent sSMC.Molecular cytogenetic techniques are necessary to the diagnosis.

Application of aCGH technology in diagnosing small supernumerary marker chromosome / 国际检验医学杂志

Objective To explore the clinical application of array comparative genomic hybridization (aCGH) and karyotype a-nalysis in the prenatal evaluation of fetal with small supernumerary marker chromosome (sSMC) .Methods One case was indenti-fied with de novo small supernumerary marker chromosome .G-banding analysis indicated that the fetus had a karyotype of 47 , XY ,+Mar .aCGH was used to define the precise location and size of de novo chromosome .Results aCGH revealed that there was 2 .03 Mb duplication from 15q11 .1-q11 .2 in the fetus .aCGH revealed the presence of small supernumerary marker chromosome . Conclusion The technologies of aCGH can be used for identifying the origin of small supernumerary marker chromosome and defi-ning the loci of the chromosome .Combined with the karyotype analysis ,it can be applied to genetics analysis and prenatal diagnosis .

Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study.

BACKGROUND: Recurrent pregnancy loss is a common occurrence and a matter of concern for couples planning the pregnancy. Chromosomal abnormalities, mainly balanced rearrangements, are common in couples with repeated miscarriages. PURPOSE: The purpose of this study is to evaluate the contribution of chromosomal anomalies causing repeated spontaneous miscarriages and provide detailed characterization of a few structurally altered chromosomes. MATERIALS AND METHODS: A retrospective cytogenetic study was carried out on 4859 individuals having a history of recurrent miscarriages. The cases were analyzed using G‑banding and fluorescence in situ hybridization wherever necessary. RESULTS: Chromosomal rearrangements were found in 170 individuals (3.5%). Translocations were seen in 72 (42.35%) cases. Of these, reciprocal translocations constituted 42 (24.70%) cases while Robertsonian translocations were detected in 30 (17.64%) cases. 7 (4.11%) cases were mosaic, 8 (4.70%) had small supernumerary marker chromosomes and 1 (0.6%) had an interstitial microdeletion. Nearly, 78 (1.61%) cases with heteromorphic variants were seen of which inversion of Y chromosome (57.70%) and chromosome 9 pericentromeric variants (32.05%) were predominantly involved. CONCLUSIONS: Chromosomal analysis is an important etiological investigation in couples with repeated miscarriages. Characterization of variants/marker chromosome enable calculation of a more precise recurrent risk in a subsequent pregnancy thereby facilitating genetic counseling and deciding further reproductive options.

Another small supernumerary marker chromosome derived from chromosome 9 in a Klinefelter patient / Otro cromosoma marcador supernumerario pequeño derivado del cromosoma 9 en un paciente con el síndrome de Klinefelter

Marker chromosomes are very rare in Klinefelter patients and phenotypic findings are related to the affected chromosomal region. The phenotypic effects of small supernumerary marker chromosomes (sSMC) range from multiple malformations/mental retardation to no effect (ie a normal phenotype). This wide spectrum of phenotypes is due to the origin, structure and gene content of the marker chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al in 2005. The present case was referred for chromosomal analysis because of dysmorphic features, speech delay and mild mental retardation. Conventional cytogenetic analysis revealed the 47 XXY karyotype in 17 metaphases and the 48 XXY + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH) analysis to identify the marker chromosome was performed using the LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this is the second case of Klinefelter syndrome with a small supernumerary marker chromosome derived from chromosome 9.

Los cromosomas marcadores son muy raros en los pacientes de Klinefelter, y los hallazgos fenotípicos se relacionan con la región cromosomática afectada. Los efectos fenotípicos de los cromosomas marcadores supernumerarios pequeños (sSMC) van desde el retraso mental y las malformaciones múltiples hasta la ausencia total de efectos (es decir, un fenotipo normal). Este amplio espectro de fenotipos se debe al origen, estructura y contenido del gen del cromosoma marcador. El primer caso de síntoma Klinefelter con sSMC 9 fue publicado por Liehr et al en 2005. El caso presente fue remitido para análisis cromosomático debido a rasgos dismórficos, retraso del habla, y retardo mental ligero. El análisis citogenético convencional reveló el cariotipo 47 XXY en 17 metafases y el cariotipo marcador 48 XXY+ en ocho metafases. El análisis mediante hibridación fluorescente in situ (FISH) para identificar el cromosoma marcador se realizó usando la sonda LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe). Un mosaicismo de trisomía 9 parcial fue confirmado en este paciente. Hasta donde sabemos, éste es el segundo caso de síndrome de Klinefelter con un cromosoma marcador supernumerario pequeño derivado del cromosoma 9.

Familial small supernumerary marker chromosome (sSMC) (14)(:p11-q11:) in a child with translocation down syndrome.

We report a case of familial small supernumerary marker chromosome (sSMC) in a child with translocation Down syndrome (DS)and mother.The GTG-banded chromosomal analysis of DS child revealed 47,XY,+21,+mar and mother karyotype was 47,XX,+mar.The GTG-banded sSMC had a similar morphology of small acrocentric chromosomes .Fluorescence in situ hybridization (FISH)evaluation of sSMC using centromere probes(13/21,14/22,22)confirmed sSMC as derivative chromosome 14.The sSMC was not specifically stained with whole chromosome paint and arm-specific probes for chromosome 14;thus it has been described as der(14)(:p11-q11:).The phenotypic changes were not evident, may be due to trisomy condition in the child or the sSMC contain repetitive sequences.