Mechanisms for the Generation of Two Quadruplications Associated with Split-Hand Malformation
| Autor: | Shen, Gu, Jennifer E, Posey, Bo, Yuan, Claudia M B, Carvalho, H M, Luk, Kelly, Erikson, Ivan F M, Lo, Gordon K C, Leung, Curtis R, Pickering, Brian H Y, Chung, James R, Lupski |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Base Sequence DNA Copy Number Variations Genome Human Molecular Sequence Data Infant Sequence Analysis DNA Article Pedigree 14-3-3 Proteins Alu Elements Genetic Loci Chromosome Duplication Basic Helix-Loop-Helix Transcription Factors Humans Female Hand Deformities Congenital Sequence Alignment Aged Chromosomes Human Pair 17 |
| Zdroj: | Human mutation. 37(2) |
| ISSN: | 1098-1004 |
| Popis: | Germline copy-number variants (CNVs) involving quadruplications are rare and the mechanisms generating them are largely unknown. Previously, we reported a 20-week gestation fetus with split-hand malformation; clinical microarray detected two maternally inherited triplications separated by a copy-number neutral region at 17p13.3, involving BHLHA9 and part of YWHAE. Here, we describe an 18-month-old male sibling of the previously described fetus with split-hand malformation. Custom high-density microarray and digital droplet PCR revealed the copy-number gains were actually quadruplications in the mother, the fetus, and her later born son. This quadruplication-normal-quadruplication pattern was shown to be expanded from the triplication-normal-triplication CNV at the same loci in the maternal grandmother. We mapped two breakpoint junctions and demonstrated that both are mediated by Alu repetitive elements and identical in these four individuals. We propose a three-step process combining Alu-mediated replicative-repair-based mechanism(s) and intergenerational, intrachromosomal nonallelic homologous recombination to generate the quadruplications in this family. |
| Databáze: | OpenAIRE |
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