Unbalanced translocations of Y-chromosomal fragments harboring the sex-determining region Y gene (SRY) to the X chromosome or an autosome result in 46,XX and 45,X testicular disorders of sex development (DSD), respectively.
Testicular or ovotesticular disorders of sex development (DSD) in individuals with female karyotype (XX) lacking the SRY gene has been observed in several mammalian species, including dogs.
The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease.
We performed exome or Sanger sequencing on 79 46,XX SRY-negative individuals with either unexplained virilization or with testicular/ovotesticular disorders/differences of sex development (TDSD/OTDSD).
We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD).
Of particular interest is a rare XX DSD subtype in which individuals are negative forSRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family.
Many of the genes mutated in DSD encode transcription factors such as SRY, SOX9, NR5A1, and FOXL2, characterized by a strictly regulated spatiotemporal expression.
Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition) with dysgenic gonads.
Testicular or ovotesticular disorder of sex development (DSD) in genetic females (78,XX; SRY-negative) has been reported quite frequently in numerous dog breeds and is usually diagnosed due to the presence of female external genitalia with an enlarged clitoris.
it was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype.
Karyotyping was done and the patients were screened for underlying changes in SRY, desert hedgehog (DHH), DAX1 (NR0B1) and SF1 (NR5A1) genes, mutations in which are implicated in DSD.
Investigations of humans with disorders of sex development (DSDs) resulted in the discovery of many of the now-known mammalian sex-determining genes, including SRY, RSPO1, SOX9, NR5A1, WT1, NR0B1, and WNT4.
Although defects in this genetic cascade lead to human disorders of sex development (DSD), only a dozen DSD genes have been identified, and causes of 46,XX DSD (XX maleness) other than SRY translocation are almost completely unknown.
To evaluate fluorescence in situ hybridization (FISH) for SRY, the testis-determining gene on the Y-chromosome, in gonadal specimens from patients with intersex disorders including two older individuals presenting with Sertoli cell adenomas and clinically unsuspected androgen insensitivity syndrome (AIS).
To our knowledge, the Sry gene itself functions testicular determination in almost all intersex cases except true hermaphrodite, a distinguished type of intersex in a different pathogenesis.