A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis
| Autor: | Daniela Söderlund, Edgardo Reyes, Juan Pablo Méndez, Felipe Vilchis, Patricia Canto |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Embryology Adolescent Gonadal dysgenesis Biology Gonadal Dysgenesis Y chromosome medicine.disease_cause Exon Reference Values Genetics medicine Humans Hedgehog Proteins Molecular Biology Desert hedgehog Mutation Sexual differentiation Genetic Carrier Screening Infant Obstetrics and Gynecology Exons Cell Biology medicine.disease Testis determining factor Reproductive Medicine Child Preschool Karyotyping Trans-Activators Male sex differentiation Developmental Biology |
| Zdroj: | MHR: Basic science of reproductive medicine. 11:833-836 |
| ISSN: | 1460-2407 1360-9947 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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