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

Yoko Narumi, Yoko Aoki, Tetsuya Niihori, Giovanni Neri, Hélène Cavé, Alain Verloes, Caroline Nava, Maria Ines Kavamura, Nobuhiko Okamoto, Kenji Kurosawa, Raoul C.M. Hennekam, Louise C. Wilson, Gabriele Gillessen-Kaesbach, Dagmar Wieczorek, Pablo Lapunzina, Hirofumi Ohashi, Yoshio Makita, Ikuko Kondo, Shigeru Tsuchiya, Etsuro ItoKiyoko Sameshima, Kumi Kato, Shigeo Kure, Yoichi Matsubara

研究成果: Article査読

77 被引用数 (Scopus)

抄録

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 correlation. 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 inMAPK3/1 (ERK1/2) 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.

本文言語English
ページ(範囲)799-807
ページ数9
ジャーナルAmerican Journal of Medical Genetics, Part A
143
8
DOI
出版ステータスPublished - 2007 4 15

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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