Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1

Jarząbek, Katarzyna; Koda, Mariusz; Chruściel, Marcin; Kańczuga‐Koda, Luiza; Sobczyńska-Tomaszewska, Agnieszka; Rahman, Nafis; Wołczyński, Sławomir

doi:10.1016/j.jsbmb.2019.105420

Cited by 6 publications

(13 citation statements)

References 34 publications

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“…[6,13,55,72,73], and 60 (27%) AIS, NOS patients [25,26,29,44,[48][49][50]54,61,67,71,74,75,78,79,81,82]. Karyotype/fluorescent in situ hybridization analysis was performed in 58 CAIS [1,[8][9][10]12,[14][15][16][18][19][20][21][22][23][24]28,30,[32][33][34][36][37][38][39][40][41][42][43][45]…”

Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

“…Karyotype/fluorescent in situ hybridization analysis was performed in 58 CAIS [1,[8][9][10]12,[14][15][16][18][19][20][21][22][23][24]28,30,[32][33][34][36][37][38][39][40][41][42][43][45][46][47][51][52][53][55][56][57]59,62-66,68-70,80,83], 1 PAIS [55] and 14 AIS, NOS cases [29,44,48,50,81] (total: 73/225, 32%), revealing a 46,XY result and/or detecting a sex-determing region Y (SRY) in all the tested cases; additional findings included inv(9)(p12q13) (1 CAIS case) [15], and 9qh+ (1 AIS, NOS case) [29]. Table 5 highlights the reported AR mutations in our series (n = 11, 5% cases with available data); most of them were missense mut...…”

Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

“…Information about treatment-although frequently scant-was only available for 87 patients [1,7,8,[10][11][12][13][14][15][16][19][20][21][22][23][24][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][48][49][50][51][52][53][54]56,57,59,[61][62][63][64][65][66]…”

Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

“…Thirty-five cases (16%) revealed SCTs [8,15,[18][19][20]23,28,37,49,50,53,54,58,69,72,73,75,81], including one sclerosing variant [8] and a "grade 2" SCT with peritoneal and lymph node metastases [53]. The patients' age range was 8-76 (mean 36.9) years.…”

Section: Scts and Slctsmentioning

confidence: 99%

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Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli–Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review

Karseladze,

Asaturova,

Kiseleva

et al. 2024

JCM

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Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient’s gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli–Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient’s karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations—a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4–84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2–49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.

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Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

Section: Systematic Literature Review Results: Overviewmentioning

confidence: 99%

Section: Scts and Slctsmentioning

confidence: 99%

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Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli–Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review

Karseladze,

Asaturova,

Kiseleva

et al. 2024

JCM

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“…HSD17B3 encodes hydroxysteroid 17-beta dehydrogenase 3, which catalyzes the conversion of the more biologically active testosterone in the testis and is required for normal fetal development of the male genitalia. HSD17B3 expression has been reported in the Sertoli cells of the gonads in CAIS patients, which preserves the characteristics of the fetal gonad in the postpubertal testis in androgen synthesis (65). For the upregulation under elevated androgen levels in PAIS patients, it could be assumed that the expression of HSD17B3 might be modulated by the AR-targeted gene but not the product testosterone.…”

Section: Discussionmentioning

confidence: 97%

Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis

et al. 2021

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BackgroundAndrogen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.MethodsPeripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR).ResultsIn our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls.ConclusionThe present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.

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18-Year-old patient with Klinefelter syndrome (47, XXY) and complete androgen insensitivity syndrome (CAIS) – case report

Skalska

Ziółkowski

Skoczylas

et al. 2021

Gynecological Endocrinology

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Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1

Cited by 6 publications

References 34 publications

Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli–Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review

Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli–Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review

Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis

18-Year-old patient with Klinefelter syndrome (47, XXY) and complete androgen insensitivity syndrome (CAIS) – case report

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