Tags

Type your tag names separated by a space and hit enter

Eight novel mutations of the androgen receptor gene in patients with androgen insensitivity syndrome.
J Hum Genet. 2001; 46(10):560-5.JH

Abstract

Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder of male sexual differentiation caused by mutations in the androgen receptor (AR) gene. A reliable genotype-phenotype correlation in these patients does not exist as yet. Here we report the molecular studies performed on eight individuals with AIS. Exon-specific polymerase chain reaction (PCR), single-strand conformation polymorphism, and sequencing analyses, were performed in exons 2 to 8 of the AR gene. In one case, total cellular RNA was extracted from genital skin fibroblasts and reverse transcriptase-PCR was performed. Six different point mutations leading to amino acid substitutions (P682T, Q711E, G743E, F827V, H874R, D879Y), one splice-junction mutation (g-->c at +5, exon 6/intron 6), and a missense mutation without amino acid substitution (S888S) were identified. All mutations, including a de novo mutation, were previously undescribed on the steroid binding domain. Of the eight mutations identified, four led to a complete female phenotype (codons 743, 827, 874 and the donor splice site +5), two were detected in phenotypic females with partial virilization (codons 682 and 711), and two were present in phenotypic male subjects with undervirilized external genitalia, thus indicating that all of these sites determine AR functional activity.

Authors+Show Affiliations

Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México D.F., México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11587068

Citation

Chávez, B, et al. "Eight Novel Mutations of the Androgen Receptor Gene in Patients With Androgen Insensitivity Syndrome." Journal of Human Genetics, vol. 46, no. 10, 2001, pp. 560-5.
Chávez B, Méndez JP, Ulloa-Aguirre A, et al. Eight novel mutations of the androgen receptor gene in patients with androgen insensitivity syndrome. J Hum Genet. 2001;46(10):560-5.
Chávez, B., Méndez, J. P., Ulloa-Aguirre, A., Larrea, F., & Vilchis, F. (2001). Eight novel mutations of the androgen receptor gene in patients with androgen insensitivity syndrome. Journal of Human Genetics, 46(10), 560-5.
Chávez B, et al. Eight Novel Mutations of the Androgen Receptor Gene in Patients With Androgen Insensitivity Syndrome. J Hum Genet. 2001;46(10):560-5. PubMed PMID: 11587068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eight novel mutations of the androgen receptor gene in patients with androgen insensitivity syndrome. AU - Chávez,B, AU - Méndez,J P, AU - Ulloa-Aguirre,A, AU - Larrea,F, AU - Vilchis,F, PY - 2001/10/6/pubmed PY - 2002/1/5/medline PY - 2001/10/6/entrez SP - 560 EP - 5 JF - Journal of human genetics JO - J Hum Genet VL - 46 IS - 10 N2 - Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder of male sexual differentiation caused by mutations in the androgen receptor (AR) gene. A reliable genotype-phenotype correlation in these patients does not exist as yet. Here we report the molecular studies performed on eight individuals with AIS. Exon-specific polymerase chain reaction (PCR), single-strand conformation polymorphism, and sequencing analyses, were performed in exons 2 to 8 of the AR gene. In one case, total cellular RNA was extracted from genital skin fibroblasts and reverse transcriptase-PCR was performed. Six different point mutations leading to amino acid substitutions (P682T, Q711E, G743E, F827V, H874R, D879Y), one splice-junction mutation (g-->c at +5, exon 6/intron 6), and a missense mutation without amino acid substitution (S888S) were identified. All mutations, including a de novo mutation, were previously undescribed on the steroid binding domain. Of the eight mutations identified, four led to a complete female phenotype (codons 743, 827, 874 and the donor splice site +5), two were detected in phenotypic females with partial virilization (codons 682 and 711), and two were present in phenotypic male subjects with undervirilized external genitalia, thus indicating that all of these sites determine AR functional activity. SN - 1434-5161 UR - https://www.unboundmedicine.com/medline/citation/11587068/Eight_novel_mutations_of_the_androgen_receptor_gene_in_patients_with_androgen_insensitivity_syndrome_ L2 - https://biocyc.org/gene?orgid=HUMAN&id=HS09879 DB - PRIME DP - Unbound Medicine ER -