Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction
Publication year
2012Source
Human Genetics, 131, 9, (2012), pp. 1519-24ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Journal title
Human Genetics
Volume
vol. 131
Issue
iss. 9
Page start
p. 1519
Page end
p. 24
Subject
IGMD 3: Genomic disorders and inherited multi-system disordersAbstract
Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key regulator of meiotic recombination. As both recurrent genomic disorders and chromosomal non-disjunction are known to be associated with specific unusual patterns of recombination, we hypothesized a possible link between PRDM9 ZF variation and susceptibility to microdeletion syndromes and/or trisomy. We sequenced the PRDM9 ZF domain in 271 parents of patients with de novo microdeletions of known parental origin (velocardiofacial syndrome, the 17q21.31 microdeletion syndrome, Prader-Willi/Angelman syndrome and Williams-Beuren syndrome), and in 61 parents of individuals with a supernumerary X chromosome. We compared PRDM9 ZF genotype frequencies between parents in whose germ line the de novo rearrangement occurred and their spouses. We observed a significantly increased frequency (p = 0.006) of PRDM9 variants in parents who transmitted de novo 7q11.23 deletions to their offspring. These data suggest that certain PRDM9 alleles may be associated with an increased susceptibility to recurrent 7q11.23 microdeletions that cause Williams-Beuren syndrome. However, as the majority of parents who transmitted a de novo microdeletion/supernumerary X chromosome to their offspring have the common AA genotype, we conclude that none of the rearrangements we have studied are dependent on specific non-A PRDM9 alleles.
This item appears in the following Collection(s)
- Academic publications [238441]
- Faculty of Medical Sciences [90373]
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