Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome

Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome

Author Narumi, Yoko Google Scholar
Aoki, Yoko Google Scholar
Niihori, Tetsuya Google Scholar
Neri, Giovanni Google Scholar
Cave, Helene Google Scholar
Verloes, Alain Google Scholar
Nava, Caroline Google Scholar
Kavamura, Maria Ines Google Scholar
Okamoto, Nobuhiko Google Scholar
Kurosawa, Kenji Google Scholar
Hennekam, Raoul C. M. Google Scholar
Wilson, Louise C. Google Scholar
Gillessen-Kaesbach, Gabriele Google Scholar
Wieczorek, Dagmar Google Scholar
Lapunzina, Pablo Google Scholar
Ohashi, Hirofumi Google Scholar
Makita, Yoshio Google Scholar
Kondo, Ikuko Google Scholar
Tsuchiya, Shigeru Google Scholar
Ito, Etsuro Google Scholar
Sameshima, Kiyoko Google Scholar
Kato, Kumi Google Scholar
Kure, Shigeo Google Scholar
Matsubara, Yokhi Google Scholar
Institution Tohoku Univ
Univ Cattolica Sacro Cuore
Hop Robert Debre
Universidade Federal de São Paulo (UNIFESP)
Osaka Med Ctr
Res Inst Maternal & Child Hlth
Kanagawa Childrens Med Ctr
Inst Child Hlth
Univ Amsterdam
Great Ormond St Hosp Sick Children
Univ Essen Gesamthsch
Univ Klinikum Schleswig Holstein
Hosp Univ La Paz
Saitama Childrens Med Ctr
Asahikawa Med Coll
Ibaraki Prefectural Handicapped Childrens Ctr
Hirosaki Univ
Abstract Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by heart defects, a distinctive facial appearance, ectodermal abnormalities and mental retardation. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in two genes, PTPN11 and HRAS, respectively. Recently, we identified mutations in KRAS and BRAF in 19 of 43 individuals with CFC syndrome, suggesting that dysregulation of the RAS/RAF/MEK/ERK pathway is a molecular basis for CFC syndrome. the purpose of this study was to perform comprehensive mutation analysis in 56 patients with CFC syndrome and to investigate genotype-phenotype cot-relation. We analyzed KRAS, BRAF, and MAP2K1/2 (MEK1/2) in 13 new CFC patients and identified five BRAF and one MAP2K1 mutations in nine patients. We detected one MAP2K1 mutation in three patients and four new MAP2K2 mutations in four patients out of 24 patients without KRAS or BRAF mutations in the previous study [Niihori et al., 2006]. No mutations were identified in MAPK3/1(ERKI/2) in 21 patients without any mutations. in total, 35 of 56 (62.5%) patients with CFC syndrome had mutations (3 in KRAS, 24 in BRAF, and 8 in MAP2K1/2). No significant differences in clinical manifestations were found among 3 KRAS-positive patients, 16 BRAF-positive patients, and 6 MAP2K1/2-positive patients. Wrinkled palms and soles, hyperpigmentation and joint hyperextension, which have been commonly reported in Costello syndrome but not in CFC syndrome, were observed in 30-40% of the mutation-positive CFC patients, suggesting a significant clinical overlap between these two syndromes. (c) 2007 Wiley-Liss, Inc.
Keywords multiple congenital anomaly
cardio-faciocutaneous
syndrome
RAF
RAS
MEK
ERK
Costello syndrome
Noonan syndrome
Language English
Date 2007-04-15
Published in American Journal of Medical Genetics Part A. Hoboken: Wiley-liss, v. 143A, n. 8, p. 799-807, 2007.
ISSN 1552-4825 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 799-807
Origin http://dx.doi.org/10.1002/ajmg.a.31658
Access rights Closed access
Type Article
Web of Science ID WOS:000245661800004
URI http://repositorio.unifesp.br/handle/11600/29665

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