Author:
Chauhan Pooja,Rani Anjali,Singh Surya K.,Rai Amit K.
Abstract
Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder with a 46,XY karyotype caused by alterations in the androgen receptor<i> (AR)</i> gene. We have identified 2 mutations in the <i>AR</i> gene that resulted in complete androgen insensitivity syndrome (CAIS) in 2 unrelated cases. This study includes cytogenetics, hormonal, molecular, and bioinformatics analysis including sequencing of the <i>SRY</i> (sex-determining region Y) and <i>AR</i> genes. Mutational analysis in the first case of primary amenorrhea revealed a novel nucleotide substitution (IVS2-2A>G) in the second intron of the <i>AR</i> gene. The mutation is located in the acceptor splice site (2 nucleotides before exon 3) and caused skipping of exon 3 and formation of an abnormal protein. The second mutation (g. 98762_98764delTCT) was identified in a case of oligoamenorrhea and caused the deletion of 1 amino acid (p.∆Phe583). Both identified mutations were located in the conserved P-box region of the DNA-binding domain which is responsible for base-specific contacts with the DNA major groove. Furthermore, a hormonal imbalance was also noticed in both cases with high levels of gonadotropins like FSH and LH in both cases. The present study concluded that both identified <i>AR</i> mutations are predicted to either abolish or decrease the binding ability of the AR to androgen response elements of its downstream genes.
Subject
Developmental Biology,Embryology,Endocrinology, Diabetes and Metabolism
Cited by
6 articles.
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