AB020. What is advance in molecular diagnosis for 46,XY and 46,XX testicular disorder of sex development?

Abstract

Background The disorders of sex development (DSD) are defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. It is estimated that genital anomalies occur in 1 in 4,500 births but 1:125 boys has hypospadias. There are three broad groups: 46,XX DSD, 46,XY DSD and sex chromosome aneuploidy DSD. Recently, exome sequencing followed by analysis with a list of all known human DSD-associated genes was used to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis (E. C. Delot et al. ASHG meeting 2014). The authors identified a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding and an additional 12.5% with likely pathogenic findings. In addition, 15% had variants of uncertain clinical significance that may be reclassified as literature evolves.