title: A novel Arg615Ser mutation of androgen receptor DNA-binding domain in three 46,XY sisters with complete androgen insensitivity syndrome and bilateral inguinal hernia.
abstract: OBJECTIVE
  To present clinical, genetic, biochemical, and molecular findings in a family with three sisters with complete androgen insensitivity syndrome (CAIS) and bilateral inguinal hernia.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, India; Centre for Cellular and Molecular Biology, Hyderabad, India.
  
  
  METHODS
  A family with four sisters of female phenotype, three of whom have CAIS and bilateral inguinal hernia. Their parents also were screened.
  
  
  METHODS
  Chromosomal analyses by harvesting lymphocytes from peripheral blood sample; hormonal analysis from serum; gene sequencing.
  
  
  METHODS
  Karyotype, testosterone, follicle-stimulating hormone, and luteinizing hormone evaluation, sex-determining region Y (SRY) and androgen receptor (AR) gene sequencing.
  
  
  RESULTS
  In three sisters of karyotype 46,XY, we found a novel mutation of the single nucleotide transition C to A at position 2205 (GenBank accession number GU784857), resulting in amino acid interchange arginine to serine at codon 615 in exon 3 [R615S] (GenBank Protein_id ADD26779.1). The mother (46,XX) is a heterozygous carrier, and the fourth sister (46,XX) and father (46,XY) are normal.
  
  
  CONCLUSIONS
  We report a novel missense mutation in exon 3 of the androgen receptor gene. The nature of the mutation presented is in the highly conserved DNA-binding domain of the AR gene, implicating it in the phenotypes observed with severe undervirilization in three sisters.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Sharma
authors.forename: Rajender
authors.initials: R
authors.lastname: Singh
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Akka
authors.initials: A
authors.lastname: Jyothy
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D013734:Androgen-Insensitivity Syndrome / Q000150:complications / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000378:metabolism; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000150:complications / Q000235:genetics; D006552:Hernia, Inguinal / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D010375:Pedigree; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000235:genetics; D035781:Siblings
chemical_list: D011944:Receptors, Androgen; D012694:Serine; D004247:DNA; D001120:Arginine