Mol. Hum. Reprod. Advance Access originally published online on January 3, 2006
Molecular Human Reproduction 2005 11(11):833-836; doi:10.1093/molehr/gah216
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A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis
1Research Unit in Developmental Biology, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 2Department of Reproductive Biology and 3Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
4 To whom correspondence should be addressed at: Unidad de Investigación Médica en Biología del Desarrollo, Coordinación de Investigación en Salud, Coahuila 5, Apartado Postal A-047, Colonia Roma, CP 06703 México, DF, México. E-mail: jpmb{at}servidor.unam.mx
Aetiology of mixed gonadal dysgenesis (MGD) has not been completely elucidated. Molecular analyses have failed to demonstrate the presence of mutations in sex-determining region on Y chromosome (SRY); it has been suggested that these individuals may bear mutations in other genes involved in the testis-determining pathway. Desert hedgehog’s (DHH) importance regarding male sex differentiation has been demonstrated in various studies we describe here, for the first time, two cases of MGD in which a monoallelic single base deletion in DHH is associated with the disorder. Genomic DNA was isolated from paraffin-embedded gonad tissue from 10 unrelated patients with MGD and three controls; in addition to, DNA from peripheral blood leukocytes in 100 controls. Coding sequence abnormalities in DHH were assessed by exon-specific PCR, single-stranded conformation polymorphism (SSCP) and direct sequencing. In two patients, a heterozygous 1086delG in exon 3 was found. Comparing previously described mutations in DHH to the one observed in this study, we can affirm that the phenotypic spectrum of patients with gonadal dysgenesis due to mutations in DHH is variable. This study continues to demonstrate the importance that DHH has in mammalian male sexual differentiation, providing extended evidence that DHH constitutes a key gene in gonadal differentiation.
Key words: DHH gene/founder gene/male gonadal differentiation/MGD/mutation
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