Journal article
Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination
A Pearlman, J Loke, C Le Caignec, S White, L Chin, A Friedman, N Warr, J Willan, D Brauer, C Farmer, E Brooks, C Oddoux, B Riley, S Shajahan, G Camerino, T Homfray, AH Crosby, J Couper, A David, A Greenfield Show all
American Journal of Human Genetics | Published : 2010
Abstract
Investigations of humans with disorders of sex development (DSDs) resulted in the discovery of many of the now-known mammalian sex-determining genes, including SRY, RSPO1, SOX9, NR5A1, WT1, NR0B1, and WNT4. Here, the locus for an autosomal sex-determining gene was mapped via linkage analysis in two families with 46,XY DSD to the long arm of chromosome 5 with a combined, multipoint parametric LOD score of 6.21. A splice-acceptor mutation (c.634-8T>A) in MAP3K1 segregated with the phenotype in the first family and disrupted RNA splicing. Mutations were demonstrated in the second family (p.Gly616Arg) and in two of 11 sporadic cases (p.Leu189Pro, p.Leu189Arg) - 18% prevalence in this cohort of s..
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Awarded by National Institutes of Health
Funding Acknowledgements
This study was supported in part by the US National Institutes of Health, the Medical Research Council of the United Kingdom, and the National Health and Medical Research Council of Australia.