Genotype-phenotype correlation and identification of two novel SRD5A2 mutations in 33 Chinese patients with...

Hypospadias, a common congenital malformation of male external genitalia, is characterized mainly by an aberrant opening of the urethra on the ventral side of the penis. Depending on the severity of the disease, it can be classified into three types: anterior, middle, and posterior. In our study, 33 patients with hypospadias were recruited, including eight with anterior hypospadias and 25 with posterior hypospadias. We performed mutation analysis of the SRD5A2, AR and HSD17B3 genes in these patients. Eight different SRD5A2 mutations were detected in 15 patients with posterior hypospadias (60%, 15/25), including six previously described mutations (p.Q6X, Q71X, p.L20P, p.G203S, p.R227Q, and p.R246Q) and two novel mutations (p.G196R and p.L73Pfs^∗17). One AR gene mutation (p.A597T) was found in a patient and no HSD17B3 mutations were detected. Additionally, we carried out routine semen analyses in all adult patients. Combing mutation analysis with semen examination results, showed that whole five adult patients who carried SRD5A2 mutations had abnormal semen quality. In summary, all the detected mutations were responsible for the clinical features observed in these 16 patients. Our data suggest that mutations of the SRD5A2 gene are the main causes of posterior hypospadias and seem to affect the semen quality of adult patients, whereas mutations in AR and HSD17B3 gene were rare in these hypospadias patients. Our study expanded the SRD5A2 mutation spectrum in the Han Chinese population and provided useful information for genetic and reproductive counselling for patients with hypospadias.