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A novel androgen receptor mutation resulting in complete androgen insensitivity syndrome and bilateral Leydig cell hyperplasia.
J Androl. 2006 Jul-Aug; 27(4):510-6.JA

Abstract

Androgens drive male secondary sexual differentiation and maturation. Mutations in the androgen receptor (AR) gene cause a broad spectrum of abnormal phenotypes in humans, ranging from mild through partial to complete androgen insensitivity. We have analyzed the AR gene by using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing and have studied gonads histologically in a familial case of complete androgen insensitivity syndrome. Sequence analysis of the AR gene showed a novel C2578T missense mutation, resulting in the replacement of a highly conserved leucine residue with phenylalanine (L859F) in ligand-binding domain of the receptor. The residue L859, located in helix 10 of the androgen receptor, plays a significant role in overall architecture of ligand-binding pocket. The mutation was absent from the father, normal brother of the patients, and 100 normal males recruited in this study as controls. The inheritance of the mutation in the family clearly shows that C2578T is the underlying mutation for the eventual phenotype in the patients. Histology of patient's gonads showed Leydig cell hyperplasia, with a few or no spermatogonium. It is thought that AR gene mutations result in hormonal imbalance, resulting in the high levels of luteinizing hormone (LH) and ultimately Leydig cell hyperplasia or tumor formation. In the present study, we have reported a rare familial case of Leydig cell hyperplasia despite consistently normal LH levels. The finding will help in giving counseling to this family and prevent the transmission of the mutated X chromosome to the coming generations.

Authors+Show Affiliations

Centre for Cellular and Molecular Biology, Uppal Rd, Hyderabad 500 007, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

16582414

Citation

Singh, Rajender, et al. "A Novel Androgen Receptor Mutation Resulting in Complete Androgen Insensitivity Syndrome and Bilateral Leydig Cell Hyperplasia." Journal of Andrology, vol. 27, no. 4, 2006, pp. 510-6.
Singh R, Shastry PK, Rasalkar AA, et al. A novel androgen receptor mutation resulting in complete androgen insensitivity syndrome and bilateral Leydig cell hyperplasia. J Androl. 2006;27(4):510-6.
Singh, R., Shastry, P. K., Rasalkar, A. A., Singh, L., & Thangaraj, K. (2006). A novel androgen receptor mutation resulting in complete androgen insensitivity syndrome and bilateral Leydig cell hyperplasia. Journal of Andrology, 27(4), 510-6.
Singh R, et al. A Novel Androgen Receptor Mutation Resulting in Complete Androgen Insensitivity Syndrome and Bilateral Leydig Cell Hyperplasia. J Androl. 2006 Jul-Aug;27(4):510-6. PubMed PMID: 16582414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel androgen receptor mutation resulting in complete androgen insensitivity syndrome and bilateral Leydig cell hyperplasia. AU - Singh,Rajender, AU - Shastry,Prabhakar K, AU - Rasalkar,Avinash A, AU - Singh,Lalji, AU - Thangaraj,K, Y1 - 2006/04/01/ PY - 2006/4/4/pubmed PY - 2006/10/28/medline PY - 2006/4/4/entrez SP - 510 EP - 6 JF - Journal of andrology JO - J Androl VL - 27 IS - 4 N2 - Androgens drive male secondary sexual differentiation and maturation. Mutations in the androgen receptor (AR) gene cause a broad spectrum of abnormal phenotypes in humans, ranging from mild through partial to complete androgen insensitivity. We have analyzed the AR gene by using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing and have studied gonads histologically in a familial case of complete androgen insensitivity syndrome. Sequence analysis of the AR gene showed a novel C2578T missense mutation, resulting in the replacement of a highly conserved leucine residue with phenylalanine (L859F) in ligand-binding domain of the receptor. The residue L859, located in helix 10 of the androgen receptor, plays a significant role in overall architecture of ligand-binding pocket. The mutation was absent from the father, normal brother of the patients, and 100 normal males recruited in this study as controls. The inheritance of the mutation in the family clearly shows that C2578T is the underlying mutation for the eventual phenotype in the patients. Histology of patient's gonads showed Leydig cell hyperplasia, with a few or no spermatogonium. It is thought that AR gene mutations result in hormonal imbalance, resulting in the high levels of luteinizing hormone (LH) and ultimately Leydig cell hyperplasia or tumor formation. In the present study, we have reported a rare familial case of Leydig cell hyperplasia despite consistently normal LH levels. The finding will help in giving counseling to this family and prevent the transmission of the mutated X chromosome to the coming generations. SN - 0196-3635 UR - https://www.unboundmedicine.com/medline/citation/16582414/A_novel_androgen_receptor_mutation_resulting_in_complete_androgen_insensitivity_syndrome_and_bilateral_Leydig_cell_hyperplasia_ L2 - https://doi.org/10.2164/jandrol.05181 DB - PRIME DP - Unbound Medicine ER -