Mutation analysis of androgen receptor gene: Multiple uses for a single test

Shojaei, Azadeh; Behjati, Farkhondeh; Ebrahimzadeh-Vesal, Reza; Razzaghy-Azar, Maryam; Derakhshandeh-Peykar, Pupak; Izadi, Pantea; Kajbafzadeh, Abdol‐Mohammad; Dowlatih, Mohammad-Ali; Karami, Fatemeh; Bazzaz, Javad Tavakkoly

doi:10.1016/j.gene.2014.09.038

Cited by 3 publications

(3 citation statements)

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“…This study showed two mutations occurring on AR gene exon 7, and p.R841H change was previously reported in a PAIS Iranian family (Shojaei et al, ). p.R832Q was first reported in an Iranian CAIS family.…”

Section: Discussionsupporting

confidence: 82%

Molecular investigation of mutations in androgen receptor and 5‐alpha‐reductase‐2 genes in 46,XY Disorders of Sex Development with normal testicular development

et al. 2019

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In this study, we aimed to determine androgen receptor (AR) and SRD5A2 gene mutations in 45 patients characterised by 46,XY Disorders of Sex Differentiation (DSD) signs with normal testicular development referred to the Children's Medical Center from February 2015 to September 2017. Karyotype and sex hormone analyses were performed. Cytogenetic investigation showed that seven patients were 46,XX DSD, six patients were chromosomal DSD and 32 patients were 46,XY DSD. Eight exons of the AR gene and five exons of the SRD5A2 gene were amplified. Two cases were affected with androgen insensitivity syndrome (AIS) (missense mutation on exon 7, position c.3637 G>A: p.R841H and position c.3610 G>A: p.R832Q), one case was affected with 5‐alpha‐reductase deficiency type 2 (missense mutation at c.578A>G: p.N193S on exon 4), and 22 cases (88%) did not demonstrate AIS or 5α‐RD2 gene abnormality. Due to the great impact of these disorders on human lifestyle, evaluation of genes involved can improve genetic counselling and therapeutic management. We focused on the AR and SRD5A2 genes in patients with 46,XY DSDs with normal testicular development referred to the Children's Medical Center from all over the country to eventually culminate in a reliable prenatal diagnosis protocol at this major referral centre giving service to a great number of families with consanguineous marriages.

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Section: Discussionsupporting

confidence: 82%

Molecular investigation of mutations in androgen receptor and 5‐alpha‐reductase‐2 genes in 46,XY Disorders of Sex Development with normal testicular development

et al. 2019

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“…The first novel substitution p.Asp840Tyr in patient 6 is located in a conserved region of ligand‐binding domain (exon 7), in which a variety of mutations could be associated with androgen insensitivity syndrome, such as p.Arg841Cys, p.Arg841Gly, p.Arg841His, p.Arg841Ser and p.Ile842Ser (Kon et al., ; Li, Li, Xu, Wang, & Shen, ; Giwercman et al., ; McPhaul et al., ; Melo et al., ; Shojaei et al., ; Szafran et al., ). These mutations (p.Arg841Cys, p.Arg841Gly, p.Arg841Ser) were also reported to be linked to PAIS in other literatures (Georget, Terouanne, Lumbroso, Nicolas, & Sultan, ; Mazen, Lumbroso, Ghaffar, Salah, & Sultan, ).…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular characteristics in 15 patients with androgen receptor gene mutations from South China

Ling

Cheng

et al. 2017

Andrologia

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A variety of mutations in the androgen receptor (AR) gene are linked to androgen insensitivity syndrome (AIS) or sexual development disorder. Here, we studied 15 patients with various degrees of disorders of genital hypoplasia from South China. Clinical data including basal hormone level, phenotype, karyotyping and SRY gene identification were documented. Exons with flanking intronic region of the AR gene were sequenced and analysed for mutations, and a total of eight mutations were identified in the AR gene. Of eight mutations, two novel mutations c.2518G>T (p.Asp840Tyr) and c.1186G>C (p.Gly396Arg) were predicted to be damaging by SIFT and Polyphen2 online software. Previously reported mutations: c.528C>A (p.Ser176Arg), c.1789G>A (p.Ala597Thr), c.2612C>T (p.Ala871Val), c.1752C>A (p.Phe584Leu), c.171_172insCTG (p.57_58insLeu) and c.2659A>G (p.Met887Val) were also detected in our subjects. Most of them are involved in hypospadias, penis dysplasia or other disorders of sexual development. A complete AIS case (p.Phe584Leu) with female phenotype and high serum concentrations of dihydrotestosterone (DHT) was also found. This study presented a wide range of spectrum of AIS (from partial AIS to complete AIS) caused by AR mutations in South China population. It suggests that further study with larger data set need to be performed to elucidate the differences of the phenotypes in our study.

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“…This study provided a deep genomic analysis using SNP array and WES data of the constitutive DNA of a patient harboring the missense c.2225G > A (p.R841H or rs9332969) mutation of the AR gene. It has been reported that the R841H protein variation influences its binding to and interactions with androgens [ 21 ]; however, this substitution does not result in complete AR functional disruption [ 22 ] and gives rise to variable expression of the AIS phenotype [ 2 , 23 ], suggesting that alterations in other genes may modulate and affect the final phenotype. Our SNP array and WES analysis of both affected cousins in this study did not reveal the presence of additional causative genetic events responsible for the PAIS phenotype, thus strongly supporting the pathogenic role of the p.R841H variant in PAIS.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

et al. 2016

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BackgroundAndrogen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described.Case presentationHere, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.ConclusionsBy pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40880-016-0115-1) contains supplementary material, which is available to authorized users.

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Mutation analysis of androgen receptor gene: Multiple uses for a single test

Cited by 3 publications

References 21 publications

Molecular investigation of mutations in androgen receptor and 5‐alpha‐reductase‐2 genes in 46,XY Disorders of Sex Development with normal testicular development

Molecular investigation of mutations in androgen receptor and 5‐alpha‐reductase‐2 genes in 46,XY Disorders of Sex Development with normal testicular development

Clinical and molecular characteristics in 15 patients with androgen receptor gene mutations from South China

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

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