Persistent Müllerian duct syndrome: A novel mutation in the Αnti-Müllerian Ηormone gene

Altıncık, Ayça; Karaca, Fahri; Önay, Hüseyin

doi:10.14310/horm.2002.1735

Cited by 5 publications

(6 citation statements)

References 10 publications

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“…Adding with our patients in China, there were 93 families with 78 different variants in AMH ( Supplementary Table 2 ) and 94 families with 80 different variants in AMHR2 have been reported ( Supplementary Table 3 ). 6 8 9 10 11 12 13 14 15 16 The relationship between the phenotypes and genotype of all patients was analyzed statistically ( ). There was no significant difference in anatomy between patients with either AMH or AMHR2 variants.…”

Section: Resultsmentioning

confidence: 99%

“…In our literature review, variants of AMH and AMHR2 were reported in 87.9% of all patients and were approximately equally distributed among the genes coding AMH and its type II receptor, AMHR2 . 6 8 9 10 11 12 13 14 15 16 Statistics indicated that AMH presented 78 different variants in 93 families, and 80 different alleles of AMHR2 were discovered in 94 families. In our Chinese patients, mutational analyses revealed possible causative variants in all patients.…”

Section: Discussionmentioning

confidence: 99%

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Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients

Tian

et al. 2022

Asian Journal of Andrology

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Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone ( AMH ) gene or the anti-Müllerian hormone receptor type 2 ( AMHR2 ) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as “pathogenic” or “likely pathogenic”, and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients

Tian

et al. 2022

Asian Journal of Andrology

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“…Two genes mutation caused this syndrome: AMH gene (on the short arm of chromosome 19) and AMHR2 gene (on the long arm of chromosome 12). AMH gene mutation caused PMDS type 1 and AMHR2 gene mutation caused PMDS type 2 (3,7). In about 16% of the cases of PMDS, there are not any detected genetic mutations (4,7).…”

Section: Discussionmentioning

confidence: 99%

“…Some authors agree with the resection of residual of Mul-lerian derivatives due to probably malignant transformation, urinary tract infection, periodic hematuria, and other urination problems. The others emphasize retaining them to protect the blood supply of testes and vas deferens (7,14). 4 Int J Cancer Manag.…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Persistent Mullerian Duct Syndrome and Review of Literature

et al. 2020

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Introduction: Persistent Mullerian duct syndrome (PMDS) is a scarce type of male pseudohermaphroditism due to anti-Mullerian hormone dysfunction. So, Mullerian duct derivatives such as the uterus, cervix, fallopian tubes, and two-thirds of the vagina are seen in a normal phenotypic and genotypic male. Considering and assessing the clinical manifestations, associated diseases, histopathology, and imaging findings can be clues in the management of such cases. Case Presentation: Here, we describe a case of PMDS with left inguinal hernia and bilateral cryptorchidism and discuss the management and review of the literature. Also, the case has a history of brain mass with a pathologic diagnosis of ganglioneuroma. Is there a correlation between PMDS and extragenital neoplasm? it needs more investigation in the future. Conclusions: Bilateral cryptorchidism could provide us with a hint toward PMDS diagnosis. However, genetic counseling will be required, particularly in parental consanguinity.

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“…One had an inguinal hernia and unilateral cryptorchidism, and the other had TTE. The genotype of AMH and AMHR2 genes are independent of the phenotype (Altincik et al, 2017 ; Hutson et al, 2014 ; Mazen et al, 2011 ; Morikawa et al, 2014 ; van der Zwan et al, 2012 ). Environmental or other genetic factors may lead to discordant phenotypes despite identical genotypes, but the specific mechanism is unclear.…”

Section: Discussionmentioning

confidence: 99%

Two novel AMHR2 gene variants in monozygotic twins with persistent Müllerian duct syndrome: A case report and functional study

Chen

Lin

Yuan

et al. 2022

Molec Gen & Gen Med

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Background Persistent Müllerian duct syndrome (PMDS) is an autosomal recessive congenital abnormality in which Müllerian derivatives, uterus, cervix, upper two‐thirds of the vagina, and fallopian tubes persist in otherwise normally virilized males. Mutations in anti‐Müllerian hormone ( AMH ) and AMH receptor type II ( AMHR2 ) genes have been identified as causative. However, functional experimental analysis of AMHR2 or AMH variants that cause PMDS is still lacking. Materials and Methods A Chinese Han family affected by PMDS was identified. To assess the history and clinical manifestations of PMDS, physical, operational, ultrasonographical, pathological, and other examinations were performed on family members. The variant screening was conducted using trio whole‐exome sequencing (trio WES) and Sanger sequencing. Complementation‐based NanoLuciferase Binary Technology (NanoBiT) was used to examine the interaction between AMH and AMHR2 variants in vivo. The effect of the two variants on the transcriptional activity of the TGFβ/BMP pathway was evaluated using a luciferase assay. Results Classic phenotypic manifestations of PMDS in a pair of identical twins were described and confirmed by genetic sequence analysis. Molecular studies revealed two novel variants c.118G > C [p.(Gly40Arg)], c.1222G > C [p.(Ala408Pro)] in the AMHR2 gene. The AMHR2 p.Gly40Arg variant reduces its ability to bind to AMH, while the p.Ala408Pro variant alters the kinase domain structure. Both variants significantly reduce TGFβ/BMP signaling. Conclusion Two missense AMHR2 variants associated with PMDS were identified. These findings provide novel insights toward better clinical evaluation and further understanding of the molecular basis of PMDS.

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Persistent Müllerian duct syndrome: A novel mutation in the Αnti-Müllerian Ηormone gene

Cited by 5 publications

References 10 publications

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients

A Rare Case of Persistent Mullerian Duct Syndrome and Review of Literature

Two novel AMHR2 gene variants in monozygotic twins with persistent Müllerian duct syndrome: A case report and functional study

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