Molecular diagnosis of 5α-reductase-2 gene mutation in two Indian families with male pseudohermaphroditism

Aim： To identify the genotype of two Indians with male pseudohermaphroditism. Methods： Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carded out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5α- reductase type 2 gene （SRDSA2） gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus. Results： We found an SRDSA2 gene mutation in exon 5, where arginine is substituted with glutamine （R246Q）, in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India. Conclusion： Identification of the R246Q mutation of the SRDSA2 gene from two unrelated Indian families possibly extends the founder gene effect.

Genetic Approaches for Sex Determination of Chinese Female with Male Pseudohermaphroditism

Male pseudohermaphroditism is a rare disorders of sex development(DSD)that is manifested by a female-like appearance or incompletely differentiated external genitalia in an individual with a Y chromosome.In this paper,we report our investigation of the case of a 33-year-old Chinese female who was diagnosed with a malignant mixed germ-cell tumor of the ovary.To confirm the sex of the female,we utilized genetic approaches to detect amelogenin and Y-STR loci.Y chromosome microdeletion was performed to identify existing deletions in the AZF regions and SRY.Chromosome karyotyping and whole-exome sequencing(WES)were then applied to reveal the deletion of sex chromosome segments and pathogenic variations in DNA sequences.Using DNA-STR genotyping,we detected both AMEL-X and AMEL-Y fragments.We also found haplotype Y-STR loci and detected all alleles.Furthermore,no microdeletion was detected in the AZF regions and SRY.The chromosome karyotyping was 46,XY.WES revealed a transversion mutation of 58T→C in the androgen receptor exon 1,which could be the pathogenic variant in this case of abnormal sexual development.Sex determination in forensic DNA typing is based on the amelogenin system.It is important that forensic biologists should master various genetic approaches to overcome the issue of gender ambiguity caused by DSDs.

S578N mutation of the androgen receptor in an adolescent with complete androgen insensitivity syndrome

Androgen insensitivity syndrome （AIS） was first .described by the American gynecologist Morris in 1953 and was mitially described＇in 82 patients, The syndrome was designated testicular feminization syndrome , because the testes produce hormones with estrogen-like actions. Clinical AIS manifestations include the appearance of normal female external genitalia without internal female genital organs.