Germinal Mosaicism in Noonan Syndrome: A Family With Two Affected Siblings of Normal Parents

被引：6

作者：

Elalaoui, Siham Chafai ^{[1
]}

Kraoua, Lilia ^{[2
]}

Liger, Celine ^{[2
]}

Ratbi, Ilham ^{[1
,3
]}

Cave, Helene ^{[2
]}

Sefiani, Abdelaziz ^{[1
,3
]}

机构：

[1] Natl Inst Hyg, Dept Med Genet, Rabat, Morocco

[2] Univ Paris 07, Hop Robert Debre, APHP, Dept Genet, Paris, France

[3] Univ Mohammed V Souissi, Fac Med & Pharm, Ctr Human Genet, Rabat, Morocco

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2010年 / 152A卷 / 11期

关键词：

Noonan syndrome; PTPN11; germline mosaicism; COSTELLO-SYNDROME; PTPN11; MUTATIONS; MOLECULAR CHARACTERIZATION; SOMATIC MOSAICISM; LINE MOSAICISM; GERMLINE; PHENOTYPE; TRANSMISSION; DISORDERS; SPECTRUM;

D O I：

10.1002/ajmg.a.33685

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Noonan syndrome (NS; OMIM 163950) is an autosomal dominant disorder with variable clinical expression and genetic heterogeneity. Clinical manifestations include characteristic facial features, short stature, and cardiac anomalies. Mutations in protein-tyrosine phosphatase, non-receptor-type 11 (PTPN11), encoding SHP-2, account for about half of NS patients. We report on a Moroccan family with two children with NS and apparently unaffected parents. The molecular studies showed the heterozygous mutation c.922A > Gof PTPN11 gene in the two affected sibs. Neither the parents, nor the oldest brother carries this mutation in hematologic cells. The mutation was also absent in buccal epithelial cells and fingernails of both parents. We believe this is the first report of germ cell mosaicism in NS and suggest an empirical risk for recurrence of that is less than 1%. (C) 2010 Wiley-Liss, Inc.

引用

页码：2850 / 2853

页数：4

共 24 条

[11] Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway:: genotype-phenotype relationships and overlap with Costello syndrome [J].

Nava, Caroline ;

Hanna, Nadine ;

Michot, Caroline ;

Pereira, Sabrina ;

Pouvreau, Nathalie ;

Niihori, Tetsuya ;

Aoki, Yoko ;

Matsubara, Yoichi ;

Arveiler, Benoit ;

Lacombe, Didier ;

Pasmant, Eric ;

Parfait, Beatrice ;

Baumann, Clarisse ;

Heron, Delphine ;

Sigaudy, Sabine ;

Toutain, Annick ;

Rio, Marlene ;

Goldenberg, Alice ;

Leheup, Bruno ;

Verloes, Alain ;

Cave, Helene .

JOURNAL OF MEDICAL GENETICS, 2007, 44 (12) :763-771

[12] The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling [J].

Neel, BG ;

Gu, HH ;

Pao, L .

TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (06) :284-293

[13]

NOONAN JA, 1963, J PEDIATR-US, V63, P468

[14] Noonan and cardio-facio-cutaneous syndromes:: two clinically and genetically overlapping disorders [J].

Nystrom, A.-M. ;

Ekvall, S. ;

Berglund, E. ;

Bjorkqvist, M. ;

Braathen, G. ;

Duchen, K. ;

Enell, H. ;

Holmberg, E. ;

Holmlund, U. ;

Olsson-Engman, M. ;

Anneren, G. ;

Bondeson, M-L .

JOURNAL OF MEDICAL GENETICS, 2008, 45 (08) :500-506

[15]

PENROSE LS, 1955, LANCET, V2, P312

[16] Germline gain-of-function mutations in RAF1 cause Noonan syndrome [J].

Razzaque, M. Abdur ;

Nishizawa, Tsutomu ;

Komoike, Yuta ;

Yagi, Hisato ;

Furutani, Michiko ;

Amo, Ryunosuke ;

Kamisago, Mitsuhiro ;

Momma, Kazuo ;

Katayama, Hiroshi ;

Nakagawa, Masao ;

Fujiwara, Yuko ;

Matsushima, Masaki ;

Mizuno, Katsumi ;

Tokuyama, Mika ;

Hirota, Hamao ;

Muneuchi, Jun ;

Higashinakagawa, Toru ;

Matsuoka, Rumiko .

NATURE GENETICS, 2007, 39 (08) :1013-1017

[17] Germline BRAF Mutations in Noonan, LEOPARD, and Cardiofaciocutaneous Syndromes: Molecular Diversity and Associated Phenotypic Spectrum [J].

Sarkozy, Anna ;

Carta, Claudio ;

Moretti, Sonia ;

Zampino, Giuseppe ;

Digilio, Maria C. ;

Pantaleoni, Francesca ;

Scioletti, Anna Paola ;

Esposito, Giorgia ;

Cordeddu, Viviana ;

Lepri, Francesca ;

Petrangeli, Valentina ;

Dentici, Maria L. ;

Mancini, Grazia M. S. ;

Selicorni, Angelo ;

Rossi, Cesare ;

Mazzanti, Laura ;

Marino, Bruno ;

Ferrero, Giovanni B. ;

Silengo, Margherita Cirillo ;

Memo, Luigi ;

Stanzial, Franco ;

Faravelli, Francesca ;

Stuppia, Liborio ;

Puxeddu, Efisio ;

Gelb, Bruce D. ;

Dallapiccola, Bruno ;

Tartaglia, Marco .

HUMAN MUTATION, 2009, 30 (04) :695-702

[18] Germline KRAS mutations cause Noonan syndrome [J].

Schubbert, S ;

Zenker, M ;

Rowe, SL ;

Böll, SB ;

Klein, C ;

Bollag, G ;

van der Burgt, I ;

Musante, L ;

Kalscheuer, V ;

Wehner, LE ;

Nguyen, H ;

West, B ;

Zhang, KYJ ;

Sistermans, E ;

Rauch, A ;

Niemeyer, CM ;

Shannon, K ;

Kratz, CP .

NATURE GENETICS, 2006, 38 (03) :331-336

[19] Male-to-Male Transmission of Costello Syndrome: G12S HRAS Germline Mutation inherited from a Father With Somatic Mosaicism [J].

Sol-Church, Katia ;

Stabley, Deborah L. ;

Demmer, Laurie A. ;

Agbulos, Abigail ;

Lin, Angela E. ;

Smoot, Leslie ;

Nicholson, Linda ;

Gripp, Karen W. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2009, 149A (03) :315-321

[20] Paternal germline origin and sex-ratio distortion in transmission of PTPN11 mutations in Noonan syndrome [J].

Tartaglia, M ;

Cordeddu, V ;

Chang, H ;

Shaw, A ;

Kalidas, K ;

Crosby, A ;

Patton, MA ;

Sorcini, M ;

van der Burgt, I ;

Jeffery, S ;

Gelb, BD .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (03) :492-497

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