A novel Arg615Ser mutation of androgen receptor DNA-binding domain in three 46,XY sisters with complete androgen insensitivity syndrome and bilateral inguinal hernia.
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.
Sharma
Vikas
V
Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, India.
Singh
Rajender
R
Thangaraj
Kumarasamy
K
Jyothy
Akka
A
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
D011944:Receptors, Androgen; D012694:Serine; D004247:DNA; D001120:Arginine