A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Abstract

Children with intellectual disability, dysmorphic features, malformations and/or growth abnormalities frequently display normal karyotypes. Recent studies have shown that genome-wide single nucleotide polymorphism (SNP) arrays can be effective in detecting abnormalities involving copy number variation (CNV), deletions, duplications and loss of heterozygosity (LOH) that routine cytogenetic tests fail to identify. Five patients with various degrees of intellectual disability and/or dysmorphic features and other malformations were whole-genome genotyped using the Human-1 Genotyping BeadChip – Exon-Centrix 100K SNP arrays (Illumina). All patients had undergone routine cytogenetic testing; four patients had normal karyotypes, while one patient had an apparently balanced complex translocation involving chromosomes 1q25, 1q32, 2q23, 7q22 and 16q24. We detected deletions on chromosome 1q44 and 13q31.1 in one patient, and LOH of the entire chromosome 2 in another patient, both with cytogenetically normal karyotypes. The patient with the complex translocation had a deletion on chromosome 7q22.2-22.3, which is in conjunction with one of the translocation breakpoints. Our findings provide further evidence of there being a critical region for the development of microcephaly and corpus callosum abnormalities in children with distal 1q deletions. We have also shown that apparently balanced complex translocations might not be balanced at the DNA level, and we report the fourth case of paternal uniparental disomy of chromosome 2. The results of this study suggest that it may be desirable to investigate idiopathic mental retardation using genome-wide SNP arrays, in conjunction with other cytogenetic and molecular techniques.

Phenotypic Spectrum and Extent of DNA Methylation Defects Associated with Multilocus Imprinting Disturbances

“…Notably, our patient shows an overlapping phenotypic spectrum with the reports of the last category [42,43]. However, the family of our patient is consanguineous and his two siblings, in whom UPD (2) pat is excluded, present with partly overlapping phenotypic features (compare Supplementary Appendix).…”

Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype

“…Chromosomal microarray revealed UPD2 which could lead to her phenotype through three primary mechanisms: imprinting, homozygous CNVs, or unmasking of rare pathogenic sequence variants. There are 19 cases of UPD2 reported in the literature (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Importantly, cases of both maternal and paternal UPD2 have been reported in individuals with normal phenotypes, suggesting that imprinting is an unlikely mechanism by which UPD is causing this patient's phenotype (15,22).…”

Complete Paternal Uniparental Disomy of Chromosome 2 in an Asian Female Identified by Short Tandem Repeats and Whole Genome Sequencing

“…1 ). Actually, using next-generation sequencing technology, many UPD cases had previously been detected by whole exome sequencing and WGS [Talseth-Palmer et al, 2009;Keller et al, 2010;Carmichael et al, 2013;Liu et al, 2015]. We demonstrated that the mismatch of STRs between a child and the parents is not always caused by nonrelated parents.…”