Purpose: Disorders of sex development (DSD) have been linked with gene defects that lead to gonadal dysgenesis. Herein, we aimed at identifying the genetic cause of gonadal dysgenesis in a patient with primary amenorrhoea and 46,XY karyotype from a consanguineous family.
Methods and Results: Whole exome sequencing (WES) was performed and revealed in homozygosity the rare and only once reported p.Arg164Pro missense mutation in exon 2 of the desert hedgehog (DHH) gene. Sanger sequencing was used to validate this candidate variant both in the patient, the parents and two other siblings. Both brother and sister of the index patient were found negative for the p.Arg164Pro mutation while the consanguineous parents were found to carry the mutation in the heterozygous state. Both the parents and the unaffected siblings showed no reproductive malformations.
Conclusions: Defects in the desert hedgehog (DHH) gene have been reported as a very rare cause of DSD and this report increases the number of 46,XY gonadal dysgenesis cases. Additionally, the present study highlights the importance of genetic validation of patients with DSD since might alleviate considerable psychological distress both in the patient and the parents.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology