Phenotypic Variation in 46,XX Disorders of Sex Development due to the NR5A1 p.R92W Variant: A Sibling Case Report and Literature Review

被引：12

作者：

Takasawa, Kei ^{[1
]}

Igarashi, Maki ^{[3
]}

Ono, Makoto ^{[1
]}

Takemoto, Akira ^{[2
]}

Takada, Shuji ^{[4
]}

Yamataka, Atsuyuki ^{[5
]}

Ogata, Tsutomu ^{[3
,6
]}

Morio, Tomohiro ^{[1
]}

Fukami, Maki ^{[3
]}

Kashimada, Kenichi ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Tokyo, Japan

[2] Tokyo Med & Dent Univ, Dept Human Pathol, Tokyo, Japan

[3] Juntendo Univ, Sch Med, Dept Mol Endocrinol, Tokyo, Japan

[4] Juntendo Univ, Natl Res Inst Child Hlth & Dev, Sch Med, Dept Syst BioMed, Tokyo, Japan

[5] Juntendo Univ, Sch Med, Dept Pediat Gen & Urogenital Surg, Tokyo, Japan

[6] Hamamatsu Univ, Sch Med, Dept Pediat, Hamamatsu, Shizuoka, Japan

来源：

SEXUAL DEVELOPMENT | 2017年 / 11卷 / 5-6期

基金：

日本学术振兴会;

关键词：

46; XX DSD; NR5A1; R92W; Sibling; FACTOR-I NR5A1; DIFFERENTIATION; INDIVIDUALS; DISEASE; SF-1;

D O I：

10.1159/000485868

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recently, a heterozygous missense mutation in NR5A1, p.R92W, was identified as a cause of 46,XX testicular/ovo-testicular disorders of sexual development (DSD). We report a sibling pair with 46, XX DSD due to an NR5A1 mutation with distinct phenotypes, including external and internal genitalia and gonads, for whom different rearing sexes were selected. Thus, the phenotypes of p.R92W vary, even within a family. The father of the patients showed oligozoospermia with the p.R92W mutation, suggesting that in 46,XY individuals, the mutation would cause various gonadal phenotypes. We review and discuss the general role of the R92W mutation in sexual development. (C) 2018 S. Karger AG, Basel

引用

页码：284 / 288

页数：5

共 11 条

[1] NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development [J].

Baetens, Dorien ;

Stoop, Hans ;

Peelman, Frank ;

Todeschini, Anne-Laure ;

Rosseel, Toon ;

Coppieters, Frauke ;

Veitia, Reiner A. ;

Looijenga, Leendert H. J. ;

De Baere, Elfride ;

Cools, Martine .

GENETICS IN MEDICINE, 2017, 19 (04) :367-376

[2] A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development [J].

Bashamboo, Anu ;

Donohoue, Patricia A. ;

Vilain, Eric ;

Rojo, Sandra ;

Calvel, Pierre ;

Seneviratne, Sumudu N. ;

Buonocore, Federica ;

Barseghyan, Hayk ;

Bingham, Nathan ;

Rosenfeld, Jill A. ;

Mulukutla, Surya Narayan ;

Jain, Mahim ;

Burrage, Lindsay ;

Dhar, Shweta ;

Balasubramanyam, Ashok ;

Lee, Brendan ;

Dumargne, Marie-Charlotte ;

Eozenou, Caroline ;

Suntharalingham, Jenifer P. ;

de Silva, K. S. H. ;

Lin, Lin ;

Bignon-Topalovic, Joelle ;

Poulat, Francis ;

Lagos, Carlos F. ;

McElreavey, Ken ;

Achermann, John C. .

HUMAN MOLECULAR GENETICS, 2016, 25 (16) :3446-3453

[3] Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals [J].

Domenice, Sorahia ;

Machado, Aline Zamboni ;

Ferreira, Frederico Moraes ;

Ferraz-de-Souza, Bruno ;

Lerario, Antonio Marcondes ;

Lin, Lin ;

Nishi, Mirian Yumie ;

Gomes, Nathalia Lisboa ;

da Silva, Thatiana Evelin ;

Silva, Rosana Barbosa ;

Correa, Rafaela Vieira ;

Montenegro, Luciana Ribeiro ;

Narciso, Amanda ;

Frade Costa, Elaine Maria ;

Achermann, John C. ;

Mendonca, Berenice Bilharinho .

BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS, 2016, 108 (04) :309-320

[4] Molecular aspects of steroidogenic factor 1 (SF-1) [J].

Hoivik, Erling A. ;

Lewis, Aurelia E. ;

Aumo, Linda ;

Bakke, Marit .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2010, 315 (1-2) :27-39

[5] Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues [J].

Igarashi, Maki ;

Takasawa, Kei ;

Hakoda, Akiko ;

Kanno, Junko ;

Takada, Shuji ;

Miyado, Mami ;

Baba, Takashi ;

Morohashi, Ken-ichirou ;

Tajima, Toshihiro ;

Hata, Kenichiro ;

Nakabayashi, Kazuhiko ;

Matsubara, Yoichi ;

Sekido, Ryohei ;

Ogata, Tsutomu ;

Kashimada, Kenichi ;

Fukami, Maki .

HUMAN MUTATION, 2017, 38 (01) :39-42

[6] Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development [J].

Lin, L. ;

Achermann, J. C. .

SEXUAL DEVELOPMENT, 2008, 2 (4-5) :200-209

[7] A CELL-SPECIFIC NUCLEAR RECEPTOR IS ESSENTIAL FOR ADRENAL AND GONADAL DEVELOPMENT AND SEXUAL-DIFFERENTIATION [J].

LUO, XR ;

IKEDA, YY ;

PARKER, KL .

CELL, 1994, 77 (04) :481-490

[8] The p.R92W variant of NR5A1/Nr5a1 induces testicular development of 46,XX gonads in humans, but not in mice: phenotypic comparison of human patients and mutation-induced mice [J].

Miyado, Mami ;

Inui, Masafumi ;

Igarashi, Maki ;

Katoh-Fukui, Yuko ;

Takasawa, Kei ;

Hakoda, Akiko ;

Kanno, Junko ;

Kashimada, Kenichi ;

Miyado, Kenji ;

Tamano, Moe ;

Ogata, Tsutomu ;

Takada, Shuji ;

Fukami, Maki .

BIOLOGY OF SEX DIFFERENCES, 2016, 7

[9] Minireview: Steroidogenic Factor 1: Its Roles in Differentiation, Development, and Disease [J].

Schimmer, Bernard P. ;

White, Perrin C. .

MOLECULAR ENDOCRINOLOGY, 2010, 24 (07) :1322-1337

[10] DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease [J].

Suntharalingham, Jenifer P. ;

Buonocore, Federica ;

Duncan, Andrew J. ;

Achermann, John C. .

BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2015, 29 (04) :607-619

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