A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family

Decaestecker, Karel; Philibert, Pascal; Baere, Elfride De; Kaufman, Jean‐Marc; Sultan, Charles; T’Sjoen, Guy

doi:10.1016/j.fertnstert.2007.04.057

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…Third, the incidence of variants causing truncation of the receptor protein molecule is low. Patients often have the classic clinical/endocrine phenotype of CAIS [37][38][39][40]. Fourth, variants that cause ligand-specific changes are rare.…”

Section: Discussionmentioning

confidence: 99%

Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome

Cheng

Sun

et al. 2020

Bioscience Reports

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Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C>A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C>T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS.

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Section: Discussionmentioning

confidence: 99%

Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome

Cheng

Sun

et al. 2020

Bioscience Reports

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“…Клінічні варіанти синдрому нечутливості до андрогенів мають широку варіативність: від нормального чоловічого фенотипу з ізольованим безпліддям до геніталій невизначеної будови і формування повністю жіночого фенотипу (CAIS) [21]. CAIS, який раніше називали синдромом тестикулярної фемінізації, характеризується однобічними або (нерідко) двобічними паховими килами у дівчат в препубертатний період та первинною аменореєю в період статевого дозрівання [22]. Характерні риси CAIS охоплюють нормальний жіночий фенотип, нормальний розвиток молочних залоз, відсутнє або незначне оволосіння на лобку та в пахвових ділянках, відсутність матки та яєчників, а також наявність короткої піхви зі сліпим кінцем [23].…”

Section: мутації в гені Amhr2unclassified

Genetic spectrum of disorders of sex development in children in Ukraine

Globa¹,

Зелінська²,

Shcherbak³

et al. 2019

CE&ES

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“…CAIS, which has previously been termed testicular feminization syndrome ( 6 ), is characterized by unilateral or often bilateral inguinal hernias in prepubertal girls and with primary amenorrhea during puberty ( 7 ). The characteristic features of CAIS include a normal female phenotype, normal breast development, an absence of or sparse pubic and axillary hair, an absence of the uterus and ovaries, and a short blind-ending vagina ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Androgens are essential for normal male sex differentiation and are responsible for the normal development of male secondary sexual characteristics at puberty. The physiological effects of androgens are mediated by the androgen receptor (AR). Mutations in the AR gene are the most common cause of androgen insensitivity syndrome. The present study undertook a genetic analysis of the AR gene in two unrelated families affected by complete androgen insensitivity syndrome (CAIS) in China. In family 1, a previously reported nonsense mutation (G-to-A; p.W751X) was identified in exon 5 of the AR gene. In addition, a novel missense mutation was detected in exon 6 of the AR gene from family 2; this mutation resulted in a predicted amino acid change from phenylalanine to serine at codon 804 (T-to-C; p.F804S) in the ligand-binding domain (LBD) of AR. Computer simulation of the structural changes generated by the p.F804S substitution revealed marked conformational alterations in the hydrophobic core responsible for the stability and function of the AR-LBD. In conclusion, the present study identified two mutations from two unrelated Chinese families affected by CAIS. The novel mutation (p.F804S) may provide insights into the molecular mechanism underlying CAIS. Furthermore, it expands on the number of mutational hot spots in the international AR mutation database, which may be useful in the future for prenatal diagnosis and genetic counseling.

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A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family

Cited by 8 publications

References 19 publications

Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome

Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome

Genetic spectrum of disorders of sex development in children in Ukraine

Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome

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