Identification of four novel variant in the AMHR2 gene in six unrelated Turkish families
E Unal1, A A Karakaya2, A Beştaş2
1Department of Pediatric Endocrinology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. edip76@yahoo.com.
Purpose:
Persistent Müllerian duct syndrome (PMDS) is characterized by the persistence of Müllerian structures in male with normal phenotype. Most cases occur as a result of mutations in the anti-Müllerian hormone (AMH) or AMHR2 genes. In this study, we aim to discuss the results of clinical, laboratory, and molecular genetic analysis of cases detected to have AMHR2 gene mutation.
Methods:
A total of 11 cases from 6 families were included in the study. AMHR2 gene mutation analyses were performed by sequencing of the coding exons and the exon-intron boundaries of the genes. The American College of Medical Genetics guidelines were used for the classification of the detected variants.
Results:
Six of the 11 cases were admitted due to bilateral undescended testes and five cases due to inguinal hernia (three transverse testicular ectopia and two hernia uterus inguinalis). All cases had normal AMH levels. Seven different variants were identified in the six families. The variants detected in four cases were considered novel (c.78del, c.71G > A, c.1460dup, c.1319A > G). Two of the novel variants were missense (exon 2 and exon 10) mutations, one was deletion (exon 2), and one duplication (exon 11).
Conclusion:
We identified four novel mutations in the AMHR2 gene resulting in PMDS. Duplication mutation (c.1460dup) in the AMHR2 gene causing PMDS was demonstrated for the first time. The most important complications of PMDS are infertility and malignancy. Early diagnosis is vital to preventing malignancy. Vas deferens and vascular structures may be injured during orchiopexy. Therefore, patients should always be referred to experienced clinics.
Insights
Persistent Müllerian duct syndrome (PMDS) in males is often caused by AMHR2 gene mutations. This study identified four novel mutations, including a first-time reported duplication, aiding in early diagnosis and management of PMDS.
Area of Science:
- Genetics
- Endocrinology
- Pediatric Surgery
Background:
- Persistent Müllerian duct syndrome (PMDS) involves Müllerian structures in phenotypically normal males.
- Mutations in anti-Müllerian hormone (AMH) or AMH receptor type 2 (AMHR2) genes are common causes of PMDS.
Purpose of the Study:
- To analyze clinical, laboratory, and molecular genetic findings in patients with PMDS due to AMHR2 gene mutations.
- To identify and characterize novel mutations within the AMHR2 gene associated with PMDS.
Main Methods:
- Sequencing of coding exons and exon-intron boundaries of the AMHR2 gene in 11 cases from 6 families.
- Classification of identified genetic variants using American College of Medical Genetics guidelines.
Main Results:
- Six cases presented with bilateral undescended testes; five had inguinal hernias (including transverse testicular ectopia and hernia uterus inguinalis).
- All patients exhibited normal AMH levels.
- Seven distinct AMHR2 variants were found, with four novel mutations identified: c.78del, c.71G>A, c.1460dup, and c.1319A>G.
Conclusions:
- Four novel AMHR2 gene mutations were identified, contributing to the understanding of PMDS.
- A duplication mutation (c.1460dup) in AMHR2, causing PMDS, was reported for the first time.
- Early diagnosis of PMDS is crucial to prevent complications like infertility and malignancy; referral to specialized clinics is recommended for surgical procedures.
