Double-strand DNA break repair with replication slippage on two strands: a novel mechanism of deletion formation

Human Mutation
H E MacLeanJ D Zajac

Abstract

We have characterized an unusual family with two different androgen receptor (AR) gene deletions, in which we propose a novel mechanism of deletion formation has occurred. Affected individuals have the X-linked disorder androgen insensitivity syndrome, and we previously showed that different family members have deletions of different exons of the AR gene. We have now fully sequenced the deletions from affected individuals, and confirmed the presence of different deletions in different affected family members. Most affected and heterozygote individuals have a 4,430-bp deletion of exon 5 that occurred between repeated GTGGCAT motifs in introns 4 and 5. One affected hemizygous individual has a 4,033-bp deletion of exons 6 and 7 that occurred between repeated CCTC motifs in introns 5 and 7. The intron 5 breakpoint junctions of the two deletions are only 11 bp apart. Surprisingly, the maternal grandmother of the original index case was found to be mosaic for both deletional events, as well as having the normal AR gene. Karyotyping ruled out 47,XXX trisomy, indicating triple mosaicism for the two different deleted AR alleles and a normal AR allele. This triple mosaicism must have occurred early in embryonic development, as both delet...Continue Reading

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Citations

Aug 31, 2018·Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation·Pooja ChauhanAmit K Rai

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