AMH gene mutations in two Egyptian families with persistent müllerian duct syndrome

Area of Science:

• Genetics
• Endocrinology
• Pediatric Surgery

Background:

• Anti-Müllerian Hormone (AMH) is crucial for male sexual differentiation, inhibiting Müllerian duct development.
• Mutations in AMH or its receptor (AMHR2) cause Persistent Müllerian Duct Syndrome (PMDS), characterized by retained uterus and fallopian tubes in males.
• PMDS follows an autosomal recessive inheritance pattern and is clinically apparent only in males.

Purpose of the Study:

• To investigate the genetic basis of PMDS in two unrelated Egyptian families.
• To identify specific mutations in the AMH gene responsible for PMDS.
• To confirm the autosomal recessive inheritance of PMDS in these cohorts.

Main Methods:

• Clinical evaluation of affected individuals, including pelvic exploration and laparotomy.
• Measurement of Anti-Müllerian Hormone (AMH) levels.
• Direct sequencing of the coding region of the AMH gene to identify mutations.

Main Results:

• Two unrelated consanguineous Egyptian families presented with PMDS, exhibiting symptoms like undescended testes and presence of Müllerian duct derivatives.
• Affected individuals in both families exhibited very low or undetectable AMH levels.
• Two novel homozygous mutations, R95X in the first family and V12G in the second family, were identified in the AMH gene's coding region.

Conclusions:

• The study confirms that mutations in the AMH gene cause PMDS with autosomal recessive inheritance.
• The identified mutations provide further insight into the molecular mechanisms underlying PMDS.
• Molecular investigation and genetic counseling are recommended for cases of undescended testes in Egypt to facilitate early diagnosis of PMDS.