ESPE Abstracts (2019) 92 P2-275

46,XY Complete Gonadal Dysgenesis in a Familial Case with a Rare Mutation in the Desert Hedgehog (DHH) Gene

Vassos Neocleous1,2, Pavlos Fanis1,2, Feride Cinarli1,2, Anastasios Oulas3,2, George M Spyrou 3,2, Leonidas A Phylactou 1,2, Nicos Skordis 4,1,5


1Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. 2Cyprus School of Molecular Medicine, Nicosia, Cyprus. 3Bioinformatics Group, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus. 4Division of Pediatric Endocrinology, Paedi Center for specialized Pediatrics, Nicosia, Nicosia, Cyprus. 5St George's, University of London Medical School at the University of Nicosia, Nicosia, Cyprus


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.

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