A novel splice site and two known mutations of androgen receptor gene in sex-reversed XY phenotype.
Molecular characterization of 27 cytogenetically confirmed Indian XY females was attempted by screening selected regions of candidate genes namely SRY (HMG box) and the ligand-binding domain of androgen receptor (AR) (Exons 5-8). Three of the index cases showed sequence variations in exons of the AR gene: a deletion mutation in exon 6 (c.2762 del C), a substitution mutation (c.2925 C>T), and a novel splice donor site mutation (IVS5+1 g>a; exon 5/intron 5). The proband's (case VA156) mother and one of the sisters were heterozygous for the novel splice donor site mutation while the father was normal. Review of literature suggested that an alternate spice donor site could be utilized leading to an aberrant splicing resulting in a truncated receptor. This could not be validated further through reverse transcriptase-polymerase chain reaction as the patient failed to cooperate for follow-up. Of the 16 spice site variations reported in various ethnic groups, this is a novel variation in the AR gene to be associated with Androgen Insensitivity Syndrome. The proband's sister, noted to be a heterozygous carrier, has high risk of having XY female progeny; hence prenatal screening of the mutation in case of an XY fetus is recommended.
Department of Genetics, Dr. ALM. PG. Institute of Basic Medical Sciences, University of Madras, Chennai, India.
Vidya Rendheer
VR
Vasu
Balachandran
B
Saranya
Meena
M
Jayashankar
Arasambattu Kannan
AK
Munirajan
Sathiyavedu Thyagarajan
ST
Santhiya
D058531:46, XX Testicular Disorders of Sex Development / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*
D022821:RNA Splice Sites; D011944:Receptors, Androgen