Identification and characterization of a complex pure mosaic of small supernumerary marker chromosomes involving 11p11.12 → q12.1 and 19p12 → q12 regions in a child featuring multiple congenital anomalies

Fei, Xiang; Qi, Manlong; Zhao, Yanyan; Li‐Ling, Jesse

doi:10.1002/ajmg.a.34346

Cited by 3 publications

(2 citation statements)

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“…Cryptorchidism is the most common male congenital genitourinary defect. While it is a manifestation of many congenital defect syndromes [ 32 – 34 ], the majority of cases are nonsyndromic and of unclear etiology. Our previous genome-wide association analyses of SNP data suggest that cryptorchidism is associated with significant genetic heterogeneity [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

Wang

Kolon

et al. 2016

BMC Urol

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BackgroundCopy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population.MethodsGenome wide genotyping were performed in 559 cases and 1772 controls (Group 1) using Illumina HumanHap550 v1, HumanHap550 v3 or Human610-Quad platforms and in 353 cases and 1149 controls (Group 2) using the Illumina Human OmniExpress 12v1 or Human OmniExpress 12v1-1. Signal intensity data including log R ratio (LRR) and B allele frequency (BAF) for each single nucleotide polymorphism (SNP) were used for CNV detection using PennCNV software. After sample quality control, gene- and CNV-based association tests were performed using cleaned data from Group 1 (493 cases and 1586 controls) and Group 2 (307 cases and 1102 controls) using ParseCNV software. Meta-analysis was performed using gene-based test results as input to identify significant genes, and CNVs in or around significant genes were identified in CNV-based association test results. Called CNVs passing quality control and signal intensity visualization examination were considered for validation using TaqMan CNV assays and QuantStudio® 3D Digital PCR System.ResultsThe meta-analysis identified 373 genome wide significant (p < 5X10−4) genes/loci including 49 genes/loci with deletions and 324 with duplications. Among them, 17 genes with deletion and 1 gene with duplication were identified in CNV-based association results in both Group 1 and Group 2. Only 2 genes (NUCB2 and UPF2) containing deletions passed CNV quality control in both groups and signal intensity visualization examination, but laboratory validation failed to verify these deletions.ConclusionsOur data do not support that structural variation is a major cause of nonsyndromic cryptorchidism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12894-016-0180-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

Wang

Kolon

et al. 2016

BMC Urol

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“…In general, they contain centromeric heterochromatin and variable, but limited, amounts of pericentromeric euchromatin, either from the short arm, long arm, or both arms [Baldwin et al, 2008]. More recently, also sSMCs of a more complex architecture have been reported, containing material from 2 distinct chromosomes or non-contiguous regions from the same chromosome [Davidsson et al, 2010;Fei et al, 2011;Vetro et al, 2012]. The paucity of informative polymorphic DNA markers, together with chromosomal mosaicism, hampered the identification of the parental origin in cases with multiple sSMCs.…”

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confidence: 99%

Gain of FAM123B and ARHGEF9 in an Obese Man with Intellectual Disability, Congenital Heart Defects and Multiple Supernumerary Ring Chromosomes

Hochstenbach

Gijn²,

Krijtenburg³

et al. 2012

Mol Syndromol

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In a 24-year-old man with mild intellectual disability, congenital heart defects and obesity, we identified up to 4 small supernumerary marker chromosomes (sSMCs) in blood metaphases. The ring-shaped sSMCs were derived from chromosomes 11, 12 and X as well as a fourth, unidentified chromosome. In interphase nuclei of epithelial cells from the urinary tract and buccal mucosa, the presence of the r(11), r(12) and r(X) was confirmed by FISH. Using Illumina Infinium 317K SNP-arrays, we detected 3 copies of the pericentromeric regions of chromosomes 11, 12 and X. The r(X) was present in 84–89% of cells in the various tissues examined, lacks the XIST gene, but contains FAM123B, a potential dosage-sensitive candidate gene for congenital cardiac abnormalities, and ARHGEF9, a candidate gene for intellectual disability. ARHGEF9 encodes collybistin (CB), which is required for localization of the inhibitory receptor-anchoring protein gephyrin and for formation and maintenance of postsynaptic GABA_A and glycine receptors. We propose that the 2-fold increase in dosage of ARHGEF9 disturbs the stoichiometry of CB with its interacting proteins at inhibitory postsynapses. SNP alleles and short tandem repeat markers on the r(11) and r(X) were compatible with a maternal origin of both sSMCs through a meiosis II error. The sSMCs may have resulted from predivision chromatid nondisjunction, leading to anaphase lagging, followed by incomplete degradation of the supernumerary chromosomes.

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Small supernumerary marker chromosomes derived from human chromosome 11

Liehr,

Ziegler,

Person

et al. 2023

Front. Genet.

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Introduction: With only 39 reported cases in the literature, carriers of a small supernumerary marker chromosome (sSMC) derived from chromosome 11 represent an extremely rare cytogenomic condition.Methods: Herein, we present a review of reported sSMC(11), add 18 previously unpublished cases, and closely review eight cases classified as ‘centromere-near partial trisomy 11’ and a further four suited cases from DECIPHER.Results and discussion: Based on these data, we deduced the borders of the pericentric regions associated with clinical symptoms into a range of 2.63 and 0.96 Mb for chromosome 11 short (p) and long (q) arms, respectively. In addition, the minimal pericentric region of chromosome 11 without triplo-sensitive genes was narrowed to positions 47.68 and 60.52 Mb (GRCh37). Furthermore, there are apparent differences in the presentation of signs and symptoms in carriers of larger sSMCs derived from chromosome 11 when the partial trisomy is derived from different chromosome arms. However, the number of informative sSMC(11) cases remains low, with overlapping presentation between p- and q-arm-imbalances. In addition, uniparental disomy (UPD) of ‘normal’ chromosome 11 needs to be considered in the evaluation of sSMC(11) carriers, as imprinting may be an influencing factor, although no such cases have been reported. Comprehensively, prenatal sSMC(11) cases remain a diagnostic and prognostic challenge.

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Identification and characterization of a complex pure mosaic of small supernumerary marker chromosomes involving 11p11.12 → q12.1 and 19p12 → q12 regions in a child featuring multiple congenital anomalies

Cited by 3 publications

References 15 publications

Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

Gain of <b><i>FAM123B</i></b> and <b><i>ARHGEF9 </i></b>in an Obese Man with Intellectual Disability, Congenital Heart Defects and Multiple Supernumerary Ring Chromosomes

Small supernumerary marker chromosomes derived from human chromosome 11

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