Abstract
Persistent Müllerian duct syndrome (PMDS) is a rare autosomal recessive disorder of sexual development in males, defined by the presence of Müllerian remnants with otherwise normal sexual differentiation. Mutations in anti-Müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes are the main causes of PMDS. In this study, we performed molecular genetic analysis of 11 unrelated cryptorchidism patients using whole-exome sequencing and classified the variants. Three of the 11 patients had biallelic mutations in AMH or AMHR2. Case 1 carried a homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 of AMH (NM_000479 transcript), which is a frameshift mutation, leading to the loss of function of AMH. Case 2 carried compound heterozygous mutations; c.494_502del (p.I165_A168delinsT) in exon 4 and g.6147C>A of AMHR2 (NM_001164690 transcript). Case 3 carried compound heterozygous mutations; c.G1168A (p.E390K) in exon 9 and c.A1315G (p.M439V) in exon 10 of AMHR2 (NM_001164690 transcript). All three patients were admitted due to azoospermia- and oligospermia-caused infertility. They were furtherly diagnosed with PMDS, as pelvic magnetic resonance imaging revealed the presence of Müllerian remnants. Our study suggests that PMDS and genetic analysis should be considered during the differential diagnosis of cryptorchidism.
Highlights
Persistent Müllerian duct syndrome (PMDS, MIM#261550) is a rare autosomal recessive disorder of sexual development that affects males; it is defined by the presence of Müllerian remnants, normal karyotype (46, XY), and male external genitalia [1]
Mutations in Anti-Müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes are the main causes of PMDS [6]
Among the 11 cryptorchidism patients, three had mutations in either AMH or AMHR2, and these three patients were diagnosed with PMDS because pelvic magnetic resonance imaging (MRI) revealed the presence of Müllerian remnants
Summary
Persistent Müllerian duct syndrome (PMDS, MIM#261550) is a rare autosomal recessive disorder of sexual development that affects males; it is defined by the presence of Müllerian remnants (i.e., fallopian tubes, uterus, and upper vagina), normal karyotype (46, XY), and male external genitalia [1]. Müllerian structures completely vanish as a result of the effects of AMH during the tenth week of fetal development, which mediates normal sexual differentiation in males [3,4], while Müllerian ducts differentiate into fallopian tubes, uterus, and upper vagina in females in the absence of AMH secretion or activity [5]. About 88% of PMDS cases are caused by compound heterozygous or homozygous mutations in AMH or AMHR2, while the remaining 12% of cases that cannot be genetically diagnosed are categorized as idiopathic [7]. There are no differences in the creativecommons.org/licenses/by/
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