Whole Exome Sequencing Identifies a c.C2566T Mutation in the Androgen Receptor in a Chinese Family

Whole exome sequencing (WES) is one of the most valuable tools for the detection of Mendelian diseases in clinical laboratory. We performed WES for a family of 46,XY disorders of gender development and compared the applicability of public databases for the subsequent phenotype studies of WES-identified mutations.

DNA samples from the two patients were analyzed by WES. The mutated protein was studied using the HomoloGene database, Polyphen2, and SIFT. The phenotype of the mutation was studied using ClinVar, the androgen receptor gene mutations database, AR database at Leiden Open Variation Database, and PubMed.

A c.C2566T (p.R856C) mutation in the androgen receptor gene was detected for the patients. The in silico studies indicated that the p.R856C mutation is deleterious to the function of the androgen receptor. Unlike those of other databases, the variations listed in the androgen receptor gene mutations database were classified as complete androgen insensitivity-, partial androgen insensitivity-, or mild androgen insensitivity-relevant according to their clinical phenotype. In addition, the publications of the collected mutations in the androgen receptor gene mutations database are complete and easily accessible, which facilitates in depth studies of clinically identified mutations.

We identified a c.C2566T (p.R856C) mutation of the AR gene in cases of familial complete androgen insensitivity by WES, and provided genetic counseling to related family members. This is the first study reporting this mutation in Chinese patients. We also compared the applicability of several public databases for phenotype studies of clinically identified Androgen Receptor mutations and suggest that the androgen receptor gene mutations database best satisfies clinical demands.