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Horm Metab Res 2017; 49(01): 36-42
DOI: 10.1055/s-0042-114778
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis

Vasundhera Chauhan
1   Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
,
Viveka P. Jyotsna
1   Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
,
Vandana Jain
2   Division of Paediatric Endocrinology, Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India
,
Rajesh Khadgawat
1   Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
,
Rima Dada
3   Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations
Further Information

Publication History

received 24 April 2016

accepted 28 July 2016

Publication Date:
06 October 2016 (online)

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Abstract

46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

Key words

46,XY gonadal dysgenesis - genes - mutation - molecular diagnosis
 

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