Mutation of the androgen receptor (R840S) in an Egyptian patient with partial androgen insensitivity syndrome: Review of the literature on the clinical expression of different R840 substitutions.

Mazen, Inas; Lumbroso, Serge; Ghaffar, S. Abdel; Salah, Nesrine Ben; Sultan, Charles

doi:10.1007/bf03350912

Cited by 14 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, some missense variants may cause variable phenotypes ranging from CAIS to MAIS. The variants p.Arg841Ser and p. Phe583Ser, previously reported with PAIS phenotype, were associated with CAIS in our study [Mazen et al, 2004;Gottlieb et al, 2012]. Intriguingly, phenotypic variations were observed among affected family members in PAIS (P4 and P7) but not in CAIS (P12 and P15) [Boehmer et al, 2001a].…”

Section: Discussionsupporting

confidence: 72%

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India

Arya¹,

Barnabas²,

Lila³

et al. 2021

Sex Dev

View full text Add to dashboard Cite

The study aimed to analyze clinical and hormonal phenotype,and genotype in patients with genetically proven androgen insensitivity syndrome (AIS) from Western India. Index patients with pathogenic variants in the androgen receptor (AR) gene were identified from a consecutive 46,XY DSD cohort (n = 150) evaluated with clinical exome sequencing, and their genetically-proven affected relatives were also included. In sum, 15 index cases (9 complete AIS [CAIS] and 6 partial AIS [PAIS]) were identified making AIS the second most common (10%) cause of 46,XY DSD, next to 5α-reductase 2 deficiency (n = 26; 17.3%). Most patients presented late in the postpubertal period with primary amenorrhoea in CAIS (89%) and atypical genitalia with gynecomastia in PAIS (71.4%). All CAIS were reared as females and 83.3% of PAIS as males with no gender dysphoria. Four of 6 patients with available testosterone to dihydrotestosterone ratio had a false elevation (>10). Metastatic dysgerminoma was seen in 1 patient in CAIS, while none in the PAIS group had malignancy. Fifteen different (including 6 novel) pathogenic/likely pathogenic variants in AR were found. Nonsense and frameshift variants exclusively led to CAIS phenotype, whereas missense variants led to variable phenotypes. In this largest, monocentric study from the Asian Indian subcontinent, AIS was the second most common cause of 46,XY DSD with similar phenotype but later presentation when compared to cases in the rest of the world. The study reports 6 novel pathogenic variants in AR.

show abstract

Section: Discussionsupporting

confidence: 72%

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India

Arya¹,

Barnabas²,

Lila³

et al. 2021

Sex Dev

View full text Add to dashboard Cite

show abstract

“…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, ). In our study, patient 6 presented with hypospadias and had a p.Asp840Tyr mutation neighbouring p.Arg841 site.…”

Section: Discussionsupporting

confidence: 61%

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

Ling

Cheng

et al. 2017

Andrologia

View full text Add to dashboard Cite

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.

show abstract

“…In that period, blood samples for androgens can be taken, because LH secretion is not suppressed (152). Missense and nonsense mutations in SRD5A2 have been reported (153, 154). Androgen receptor defects can influence the number and stability of androgen receptors.…”

Section: Androgen Deficiencymentioning

confidence: 99%

Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

Honour¹

2009

JCRPE

View full text Add to dashboard Cite

Biochemical tests have been the basis for investigations of disorders affecting steroid hormones. In recent years it has been possible however to study the genes that determine functional enzymes, cofactors, receptors, transcription factors and signaling systems that are involved in the process. Analyses of mutations are available as a diagnostic service for only a few of these genes although research laboratories may be able to provide a service. Both biochemical and genetic research have brought to light new disorders. Some genes for transcription factors involved in the development of the endocrine organs have also been identified and patients with defects in these processes have been found. This paper will review general aspects of adrenal disorders with emphasis on clinical and laboratory findings. As with all endocrine investigations there are few single measurements that provide a definitive answer to a diagnosis. Timing of samples in relation to age, gender and time of day needs to be considered.Conflict of interest:None declared.

show abstract

Mutation of the androgen receptor (R840S) in an Egyptian patient with partial androgen insensitivity syndrome: Review of the literature on the clinical expression of different R840 substitutions.

Cited by 14 publications

References 24 publications

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India

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

Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

Contact Info

Product

Resources

About