title: Clinical, cytogenetic and molecular analysis of androgen insensitivity syndromes from south Indian cohort and detection and in-silico characterization of androgen receptor gene mutations.
abstract: 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.
authors.affiliation: Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamilnadu, India. Electronic address: abilash.vg@vit.ac.in.
authors.forename: Abilash
authors.initials: A
authors.lastname: V G
authors.affiliation: Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamilnadu, India.
authors.forename: Radha
authors.initials: R
authors.lastname: S
authors.affiliation: University of Madras, New No.55 (Old.No.26), Ist Main Road, Indira Nagar, Adyar, Chennai 600020, Tamilnadu, India.
authors.forename: Marimuthu
authors.initials: M
authors.lastname: K M
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
authors.forename: Thangaraj
authors.initials: T
authors.lastname: K
authors.affiliation: Human Molecular Genetics Laboratory, Department of Zoology, Bharathiar University, Coimbatore-641046, Tamil Nadu, India.
authors.forename: Arun
authors.initials: A
authors.lastname: S
authors.affiliation: Division of Biomolecules and Genetics, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamilnadu, India.
authors.forename: Nishu
authors.initials: N
authors.lastname: S
authors.affiliation: Bioinformatics Division, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamilnadu, India.
authors.forename: Mohana Priya
authors.initials: MP
authors.lastname: A
authors.affiliation: Institute of Obstetrics and Gynecology, Madras Medical College, Government Hospital for Women and Children, Egmore, Chennai 600 008, Tamil Nadu, India.
authors.forename: Meena
authors.initials: M
authors.lastname: J
authors.affiliation: Institute of Obstetrics and Gynecology, Madras Medical College, Government Hospital for Women and Children, Egmore, Chennai 600 008, Tamil Nadu, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: D
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019295:Computational Biology; D003198:Computer Simulation; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*; D055815:Young Adult
chemical_list: D011944:Receptors, Androgen
keywords: Androgen insensitivity syndrome; Androgen receptor gene; DNA-binding domain; Ligand binding domain; Polymerase chain reaction (PCR)