New mutation causing androgen insensitivity syndrome – a case report and review of literature

Maciejewska-Jeske, Marzena; Rojewska-Madziala, Patrycja; Broda, Karolina; Drabek, Karolina; Szeliga, Anna; Czyźyk, A; Malinger, Stanisław; Kostrzak, Anna; Podfigurna, Agnieszka; Bala, Gregory; Męczekalski, Błażej; Malcher, Agnieszka; Kurpisz, Maciej

doi:10.1080/09513590.2018.1529160

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…12 AIS is classed into three subtypes: (1) MAIS, which is found in males with persistent gynecomastia and/or infertility; (2) PAIS, which is found in individuals with atypical genitalia, and 3 women with CAIS are generally taller than women without the syndrome, but are-on averageshorter than the male population. 13 The case we report here was also similar in this regard. Notably, it has been reported that patients who delay gonadectomy are even taller.…”

Section: Discussionsupporting

confidence: 77%

A Case Report Based On Complete Androgen Insensitivity Syndrome

li¹,

Xiao²,

Luo³

et al. 2020

Preprint

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Background: Androgen insensitivity syndrome (AIS) is a rare disease caused by mutations in the AR gene. This results in resistance to the actions of androgen as well as a female phenotype with 46 XY. Anatomically, individuals with AIS lack both a uterus and ovaries. Case presentation: In this case report, we detail a 32-year-old patient with complete AIS (CAIS). This female patient with 46 XY genotype came to our hospital seeking surgical removal of bilateral testis. The subsequent medical history, clinical examination, imaging, and endocrine outcomes from this patient were collected and are presented here. Conclusions: Individuals with CAIS need appropriate care from doctors and support from their family. The diagnosis, treatment, and management of CAIS also requires a multidisciplinary approach.

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Section: Discussionsupporting

confidence: 77%

A Case Report Based On Complete Androgen Insensitivity Syndrome

li¹,

Xiao²,

Luo³

et al. 2020

Preprint

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“…AIS is a congenital disorder in which a defect in the AR gene leads to cellular resistance to androgens. More than 1000 AIS-causing mutations in the AR gene have been identified [24]. The types of AR gene variants include gene deletions, splice site mutations, premature stop codons and missense mutations, among others.…”

Section: Discussionmentioning

confidence: 99%

“…First, exons 5-8 and part of exon 4 encode the LBD, which includes residues 664-920 [27], and variants that cause androgen-AR-binding disorders are commonly reported in exons 4-8 [28,[29][30][31]. Patients can present complete feminization of the testes or incomplete testicular feminization [26,29,31,32]. Second, exons 2 and 3 encode the DBD, from residue 559 to 624 [27], and variants that cause binding disorders of androgen-AR complexes and DNA mainly occur in these two exons.…”

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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“…The entire microscopic picture corresponded to the clinical diagnosis of Complete Androgen Insensitivity Syndrome. More details regarding the clinical part of the case were published in a clinical presentation by Maciejewska-Jeske et al [35].…”

Section: Methodsmentioning

confidence: 99%

Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics

Malcher

Jȩdrzejczak

Stokowy

et al. 2019

IJMS

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We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C>T). Case No.3 did not reveal AR mutation; however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p < 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process.

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New mutation causing androgen insensitivity syndrome – a case report and review of literature

Cited by 5 publications

References 26 publications

A Case Report Based On Complete Androgen Insensitivity Syndrome

A Case Report Based On Complete Androgen Insensitivity Syndrome

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

Novel Mutations Segregating with Complete Androgen Insensitivity Syndrome and Their Molecular Characteristics

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