Identification of a novel mutation in the SRY gene in a 46, XY female patient.

BACKGROUND: The SRY gene encodes for a testis-specific transcription factor (TDF, testis determining factor) that plays a key role in sexual differentiation and development in males. Several SRY mutations have been described in patients with gonadal dysgenesis, accounting for 10-15% of the sex reversal cases. The reported mutations are both point mutations and deletions, mostly involving the high mobility group (HMG) box domain of SRY, which is a conserved region through the evolution, suggesting that SRY function strictly depends on the HMG box. CASE PRESENTATION: Here we describe the clinical, endocrinological and molecular data of a patient with complete 46, XY gonadal dysgenesis caused by SRY mutation located within the conserved HMG box. Using DNA direct sequencing of the SRY coding region, we identified a single nucleotide insertion at codon 89 with subsequent frameshift of the reading frame sequence, which results in a truncated protein as consequence of an introduction of a stop codon at the position 103. CONCLUSION: A novel SRY mutation has been described in a female with a gonadal dysgenesis associated with a 46, XY karyotype. The described case is of importance for genetic counseling.

The methylenetethrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility in Italy.

The 677T allele of the MTHFR gene has been suggested to represent a factor of risk for male infertility. In order to confirm this association, we investigated the presence of the 677T allele in 93 Italian infertile patients, selected after the exclusion of other possible genetic causes of infertility, and in 105 Italian fertile controls. The homozygous 677TT genotype was present in 20.4% of patients and 27.6% of controls. These results do not support an association between the MTHFR 677T allele and male infertility in Italy.