46,XY complete gonadal dysgenesis in a familial case with a rare mutation in the desert hedgehog (DHH) gene

Purpose Disorders of sex development (DSD) have been linked to gene defects that lead to gonadal dysgenesis. Herein, we aimed to identify the genetic cause of gonadal dysgenesis in a patient with primary amenorrhoea tracing it to a phenotypic female carrying a 46,XY karyotype of a consanguineous fam...

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Bibliographic Details
Published in:Hormones (Athens, Greece) Greece), 2019-09, Vol.18 (3), p.315-320
Main Authors: Neocleous, Vassos, Fanis, Pavlos, Cinarli, Feride, Kokotsis, Vasilis, Oulas, Anastasios, Toumba, Meropi, Spyrou, George M., Phylactou, Leonidas A., Skordis, Nicos
Format: Article
Language:English
Subjects:
Adult
Amenorrhea - genetics
Case Report
Consanguinity
Endocrinology
Family
Female
Gene Frequency
Gonadal Dysgenesis, 46,XY - diagnosis
Gonadal Dysgenesis, 46,XY - genetics
Hedgehog Proteins - genetics
Humans
Iraq
Medicine
Medicine & Public Health
Metabolic Diseases
Mutation, Missense
Pedigree
Young Adult
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Summary:Purpose Disorders of sex development (DSD) have been linked to gene defects that lead to gonadal dysgenesis. Herein, we aimed to identify the genetic cause of gonadal dysgenesis in a patient with primary amenorrhoea tracing it to a phenotypic female carrying a 46,XY karyotype of 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 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. Neither the parents nor the unaffected siblings showed any reproductive malformations. Conclusions Defects in the 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 this is likely to alleviate the considerable psychological distress experienced by both the patient and the parents.
ISSN:1109-3099
2520-8721
DOI:10.1007/s42000-019-00116-6