Familial Mutation in the Testis-Determining Gene SRY Shared by an XY Female and Her Normal Father
| Autor: | Eric Vilain, Manas Jain, Sathima Natarajan, S. Douglas Frasier, Brian K. Jordan |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Proband medicine.medical_specialty Gonad HMG-box Phenylalanine Endocrinology Diabetes and Metabolism Clinical Biochemistry Gonadal dysgenesis Biology medicine.disease_cause Polymerase Chain Reaction Biochemistry Fathers Endocrinology Reference Values Internal medicine Testis medicine Humans Genes sry Gene Gonadal Dysgenesis 46 XY Genetics Mutation Base Sequence Biochemistry (medical) Nuclear Proteins social sciences Sex reversal medicine.disease Sex-Determining Region Y Protein DNA-Binding Proteins Testis determining factor medicine.anatomical_structure Amino Acid Substitution HMG-Box Domains Tyrosine Female Transcription Factors |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 87:3428-3432 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.87.7.8646 |
| Popis: | In humans, mutations in the testis-determining gene SRY result in XY sex reversal with pure gonadal dysgenesis (PGD). However, only about 10-15% of the cases of PGD can be explained by mutations within the SRY open reading frame, suggesting the existence of other sex-determining genes. Although SRY is known to bind and bend DNA, its target and mode of action remain elusive. Here, we describe a novel mutation in SRY at codon 127, resulting in a tyrosine (Y) to phenylalanine (F) substitution in the protein. This sequence variant was found not only in the XY female patient but also in her father, who is a phenotypically normal male. However, this Y127F variant was not found in the SRY sequences of 93 other randomly chosen males. This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD. Furthermore, electromobility shift studies demonstrate that SRY protein harboring the Y127F variant is incapable of binding consensus SRY binding sites in vitro. Taken together, these data suggest that the Y127F variant is a novel mutation with functional consequences and not simply a polymorphism. The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway. |
| Databáze: | OpenAIRE |
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