A Novel <b><i>AMH</i></b> Missense Mutation in a Patient with Persistent Müllerian Duct Syndrome

Abstract

Persistent Müllerian duct syndrome (PMDS) is characterized by the presence of a uterus, fallopian tubes, and the upper part of the vagina in phenotypic normal male patients. Here, we report a patient diagnosed with PMDS with a novel homozygous missense mutation in the anti-Müllerian hormone (AMH) gene (single nucleotide insertion (C) at position 208 (c.208dup, p.Leu70fs)) leading to a frameshift and the introduction of a premature stop codon. Biopsy of both gonads revealed that germ cells were present in an irregular distribution. However, the absence of OCT3/4, PLAP and c-KIT expression indicated physiological maturation.

The Persistent Müllerian Duct Syndrome: An Update Based Upon a Personal Experience of 157 Cases

“…In children, testicular morphology is normal [Loeff et al, 1994;van der Zwan et al, 2012], and this is also our experience. In older patients, testes are often hypoplastic with tubular fibrosis, thickened basal membrane, and no spermatogenesis present [Mouli et al, 1988].…”

“…The first one, a stop mutation in exon 5 affecting the N-terminal domain, was detected in 1989 in 3 brothers belonging to a Moroccan family [Knebelmann et al, 1990]. Since then, we ourselves have identified 68 families with AMH mutations, and 12 have been described by other groups [Mazen et al, 2011;Nishi et al, 2012;van der Zwan et al, 2012;Morikawa et al, 2014;Nalbantoglu et al, 2015;Mazen et al, 2016]. A total of 65% of mutations are homozygous, reflecting a high rate of inbreeding in some parts of the world ( Fig.…”

Persistent Müllerian Duct Syndrome with Transverse Testicular Ectopia: A Novel Anti-Müllerian Hormone Receptor Mutation

“…In group 3, both testes are found in the same hernia sac, along with uterus and tubes (crossed or transverse testicular ectopia) (3,4). Given that the genotype of AMH and AMHR2 is not related to the phenotypes, the phenotype of our index case was consistent with group 3 (5,6). Our patient presented to the Pediatric Surgery Department with a complaint of bilateral undescended testes and was referred to us when female internal genital structures were observed at laparoscopy.…”

The Persistent Müllerian Duct Syndrome

“…There is a good correlation between the prepubertal level of serum AMH and the level of in vitro secretion: those were present in the homozygous state in the same patient, thus it is possible that one is not pathogenic. The addition of a cysteine between bases 213 and 218, reported by Josso et al [92], was wrongly regarded as a new mutation by van der Zwan et al [93] because of a 10-bp difference in numbering (beginning at the first coding base instead of the transcription initiation site used by the previous authors). Recurrent mutations are shaded and bolded.…”