Analysis of anti-Müllerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Müllerian duct syndrome

Nishi, Mirian Yumie; Domenice, Sorahia; Maciel‐Guerra, Andréa T.; Neto, Alberto Zaba; Silva, Marcia Alessandra Cavalaro Pereira da; Costa, Elaine Maria Frade; Guerra, Gil; Mendonca, Berenice B.

doi:10.1590/s0004-27302012000800002

Cited by 23 publications

(19 citation statements)

References 16 publications

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“…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.…”

Section: Amh Gene Mutationsmentioning

confidence: 90%

“…Intron 2 is the target of 2 distinct recurrent splicing mutations, the first affecting the donor and the second the acceptor site. The latter, a A>G change at the penultimate base of the intron 2, was found in 3 unrelated Brazilian patients and may represent a founder effect [Nishi et al, 2012]. Similarly, the 4 families affected by mutation c.301G>A, p.(Gly101Arg) all originate from the Middle East or Pakistan [Abduljabbar et al, 2012].…”

Section: Amh Gene Mutationsmentioning

confidence: 97%

“…Since then a total of 75 families with PMDS due to AMHRII mutations have been identified, 68 by our group. The other cases were reported in the USA [Hoshiya et al, 2003], Brazil [Nishi et al, 2012], Egypt [Mazen et al, 2016], Portugal [Rosal-Gonçalves et al, 2010], Turkey [Korkmaz et al, 2017], and Israel [Elias-Assad et al, Fig. 9.…”

Section: Amh Receptor Mutationsmentioning

confidence: 99%

See 2 more Smart Citations

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

Picard¹,

Cate

Racine³

et al. 2017

Sex Dev

124

150

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Male sex differentiation is driven by 2 hormones, testosterone and anti-müllerian hormone (AMH), responsible for the regression of müllerian ducts in male fetuses. Mutations inactivating AMH or its receptor AMHRII lead to the persistent müllerian duct syndrome (PMDS) in otherwise normally virilized 46,XY males. Our objective was to review the clinical, anatomical, and molecular features of PMDS based upon a review of the literature and upon 157 personal cases. Three clinical presentations exist: bilateral cryptorchidism, unilateral cryptorchidism with contralateral hernia, and transverse testicular ectopia. Abnormalities of male excretory ducts are frequent. Testicular malignant degeneration occurs in 33% of adults with the disorder, while cancer of müllerian derivatives is less frequent. Fertility is rare but possible if at least one testis is scrotal and its excretory ducts are intact. Eighty families with 64 different mutations of the AMH gene have been identified, mostly in exons 1, 2, and 5. AMHRII gene mutations representing 58 different alleles have been discovered in 75 families. The most common mutation, a 27-bp deletion in the kinase domain, was found in 30 patients of mostly Northern European origin. In 12% of cases, no mutation of AMH or AMHRII has been detected, suggesting a disruption of other pathways involved in müllerian regression.

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Section: Amh Gene Mutationsmentioning

confidence: 90%

Section: Amh Gene Mutationsmentioning

confidence: 97%

Section: Amh Receptor Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

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

Picard¹,

Cate

Racine³

et al. 2017

Sex Dev

124

150

View full text Add to dashboard Cite

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“…Laparoscopy is the preferred diagnostic procedure 1-4 To the best of our knowledge, as of June 2016 approximately 57 AMH mutations have been reported. 1,6 The homozygous p.C526F (c.1577G>T) mutation detected in the present case is a novel mutation.…”

Section: Discussionmentioning

confidence: 61%

“…5 Since then, more than 200 PMDS cases have been reported in the literature. [1][2][3][4]6 In this case report, we describe the clinical features of a case of PMDS type I with a novel AMH mutation.…”

Section: Introductionmentioning

confidence: 99%

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

Altıncık

Karaca

Önay

2017

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Persistence of müllerian duct structures in a genetic male with distal monosomy 10q

Tosur

Geary

Matalon

et al. 2015

American J of Med Genetics Pt A

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Persistent müllerian duct syndrome (PMD) with antimüllerian hormone (AMH) deficiency is usually associated with mutations or deletions of the AMH gene, although many cases have no identified gene association. We report on a genetic male with PMD and AMH deficiency associated with distal monosomy 10q. A term 3,230 g infant was born to a healthy 27-year-old. Fetal ultrasound had shown possible genital ambiguity. Postnatal exam showed a 0.5 cm phallus with basal meatus, normal scrotum with no palpable gonads, no vaginal orifice, and a rectal fistula with an imperforate anus. Voiding cystourethrogram with ultrasound, cystoscopy, and laparoscopy showed normal bladder, urethral orifice, distal vagina, cervix, and bilateral abdominal testis. At 24 hours of life, testosterone was within normal range with low AMH level. Chromosome microarray analysis showed 46, XY, del10(10q25.3q26.13) involving an 8.2 MB interstitial deletion. Whole exome sequencing identified a NOTCH2 variant (1p11.2). AMH sequencing revealed no abnormalities. Following multidisciplinary team and parent discussion, male gender was assigned. Testosterone treatment resulted in penile length of 1.5 cm. Bilateral orchiopexy and posterior sagittal anorectoplasty were performed at 11 months of age; rudimentary müllerian structures were identified. This observation suggests an association of 10qter elements with male differentiation including AMH expression and is similar to a patient with 46, XY, del(10q26.1) in which AMH levels were not reported. Regional candidate genes include FGFR2 (10q26.13). The possible contribution of a NOTCH2 variant cannot be excluded.

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Analysis of anti-Müllerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Müllerian duct syndrome

Abstract: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p.Arg502Leu in AMH; and p.Gly323Ser in AMHR2.

Cited by 23 publications

References 16 publications

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

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

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

Persistence of müllerian duct structures in a genetic male with distal monosomy 10q

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