AR and SRD5A2 gene mutations in a series of 51 Turkish 46,XY DSD children with a clinical diagnosis of androgen insensitivity.

46,XY disorders of sex development (DSD) are caused by disorders of gonadal development, androgen biosynthesis and receptor (AR) defects. Although, clinical/biochemical features help in distinguishing specific aetiologies, there are overlaps which necessitate molecular analyses for the definitive diagnosis. To test precision of our clinical diagnosis of androgen insensitivity (AIS) by analysing AR and then SRD5A2 genes, patients were recruited at Marmara University Hospital and molecular analyses were performed at Vall d'Hebron Research Institute. Among 101 46,XY DSD patients, 46 index and five siblings (nine complete, 42 partial) with clinical/biochemical data suggestive of AIS and stimulated T/DHT ratio <25 were selected. AR and then SRD5A2 genes were sequenced. We detected AR mutations in 11 patients [seven index and four siblings (22% of all and 15% of index patients)] and SRD5A2 mutations in six [five index and one sibling (12% of all and 11% of index)]. AR mutation detection rate was 6/9 in all CAIS and 4/7 in the index (67 and 57% respectively) and 5/42 in all PAIS and 3/40 in the index (12 and 7.5% respectively). The eight mutations detected in the AR gene were as follows: p.Q58L, p.P392S, p.R609K, p.R775H, p.R856H, p.A871A, p.V890M and p.F892L, with p.A871A and p.F892L being novel. Further six patients had SRD5A2 mutations which were as follows: p.L73WfsX59, p.Y91H, p.R171S and p.G196S, the first being novel. Hormonal data in those with AR mutations, SRD5A2 mutations and no mutations were not statistically different. In conclusion, a significant proportion of children with presumptive diagnosis of AIS has a normal AR gene. The less severe the phenotype, the less likely is the chance of demonstrating a mutation. Furthermore, a significant number of children with presumptive diagnosis of AIS have mutations in SRD5A2 gene and are clinically and biochemically indistinguishable from AIS.

Akcay T ，Fernandez-Cancio M ，Turan S ，Güran T ，Audi L ，Bereket A ... -  《-》

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development.

Ittiwut C ，Pratuangdejkul J ，Supornsilchai V ，Muensri S ，Hiranras Y ，Sahakitrungruang T ，Watcharasindhu S ，Suphapeetiporn K ，Shotelersuk V ... -  《-》

Clinical characteristics and molecular genetics of complete androgen insensitivity syndrome patients: a series study of 30 cases from a Chinese tertiary medical center.

To study the clinical characteristics and genetic basis of complete androgen insensitivity syndrome (CAIS) in patients from the People's Republic of China. CAIS patients with 46 XY karyotype produce male levels of androgens but present with female external genitalia and secondary sex characteristics. The majority of affected individuals have androgen receptor (AR) gene mutations. This case series explored clinical and molecular characteristics of CAIS patients from the People's Republic of China. Genomic DNA from peripheral blood of clinically diagnosed CAIS patients was sequenced for mutation in the androgen receptor (AR) gene and steroid 5α-reductase type 2 gene (SRD5A2). Participants were recruited from Peking Union Medical College Hospital when they came in for consultation. Thirty patients from unrelated families were recruited. Data from medical documents recording diagnosis and treatment of these patients were retrospectively collected. Patient genotypes were determined by sequencing the AR and SRD5A2 genes. Their clinical characteristics were summarized based on symptoms, hormone profiles, operative findings, and pathological results. Twenty-one patients diagnosed with CAIS had mutations in AR exons. Analysis of AR exons revealed the presence of seven novel mutations (c.58C>T, c.645_652delGGGGGCTC, c.910G>T, c.1078C>T, c.1786T>A, c.2230G>T, and c.2522G>C); of these mutations, 47.6% (10/21) were located in the ligand-binding domain. Gonadal insufficiency was found in one case of CAIS. Among the remaining nine patients, three had SRD5A2 mutations and therefore a steroid 5α-reductase deficiency. No AR or SRD5A2 mutations were detected in the other six patients. This study broadens the spectrum of known AR gene mutations responsible for CAIS, and implies that there can be more complex underlying causes of CAIS.

Zhang D ，Yao F ，Tian T ，Deng S ，Luo M ，Tian Q ... -  《-》

Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development.

Topcu V ，Ilgin-Ruhi H ，Siklar Z ，Karabulut HG ，Berberoglu M ，Hacihamdioglu B ，Savas-Erdeve S ，Aycan Z ，Peltek-Kendirci HN ，Ocal G ，Tukun FA ... -  《-》

Clinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese patients.

Liu Q ，Yin X ，Li P 《Reproductive Biology and Endocrinology》