Clinical, cytogenetic and molecular analysis of androgen insensitivity syndromes from south Indian cohort and detection and in-silico characterization of androgen receptor gene mutations

•DNA Sequence analysis of the AR gene showed three mutations•c.C1713 > G missense mutation, resulting in the replacement of a highly conserved histidine residue with glutamine (H571Q) in DNA-binding domain of androgen receptor gene.•c.A1715 > G missense mutation, resulting in the replacement of a highly conserved tyrosine residue with cysteine (Y572C) in DNA-binding domain of androgen receptor gene•c.G2599 > A missense mutation, resulting in the replacement of a highly conserved valine residue with methionine (V867M) in ligand-binding domain of androgen receptor.•The mutations H571Q and V867M were present in mothers of the patients of familial cases concluding the mutation was inherited from mother.•The novel mutation c.C1713 > G is reporting first time in androgen insensitivity syndrome.

Rare cases of 9 complete androgen insensitivity syndromes, 9 cases of partial androgen insensitivity syndromes and equal number of male control samples were selected for this study. Few strong variations in clinical features were noticed; Giemsa banded metaphase revealed a 46,XY karyotype and the frequency of chromosome aberrations were significantly higher when compared with control samples. DNA sequence analysis of the androgen receptor gene of androgen insensitivity syndromes revealed three missense mutations — c.C1713 > G resulting in the replacement of a highly conserved histidine residue with glutamine p.(His571Glu) in DNA-binding domain, c.A1715 > G resulting in the replacement of a highly conserved tyrosine residue with cysteine p.(Tyr572Cys) in DNA-binding domain and c.G2599 > A resulting in the replacement of a highly conserved valine residue with methionine p.(Val867Met) in ligand-binding domain of androgen receptor gene respectively. The heterozygous type of mutations c.C1713 > G and c.G2599 > A observed in mothers of the patients for familial cases concluding that the mutation was inherited from the mother. The novel mutation c.C1713 > G is reported first time in androgen insensitivity syndrome. In-silico analysis of mutations observed in androgen receptor gene of androgen insensitivity syndrome predicted that the substitution at Y572C and V867M could probably disrupt the protein structure and function.