Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome
| Autor: | Caroline Nava, Giovanni Neri, Louise C. Wilson, Shigeru Tsuchiya, Yoko Narumi, Nobuhiko Okamoto, Hirofumi Ohashi, Hélène Cavé, Kiyoko Sameshima, Etsuro Ito, Alain Verloes, Raoul C.M. Hennekam, Pablo Lapunzina, Yoshio Makita, Yoko Aoki, Kumi Kato, Tetsuya Niihori, Dagmar Wieczorek, Yoichi Matsubara, Gabriele Gillessen-Kaesbach, Ikuko Kondo, Kenji Kurosawa, Maria Ines Kavamura, Shigeo Kure |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatric Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Heart Defects
Congenital Proto-Oncogene Proteins B-raf medicine.medical_specialty Genotype DNA Mutational Analysis MAP Kinase Kinase 2 MAP Kinase Kinase 1 MAP2K2 Cardiofaciocutaneous syndrome medicine.disease_cause Settore MED/03 - GENETICA MEDICA Craniofacial Abnormalities Diagnosis Differential Costello syndrome Intellectual Disability Internal medicine Genetics medicine Humans Abnormalities Multiple HRAS neoplasms Genetics (clinical) Molecular Epidemiology sindrome di Costello genetica clinica business.industry sindrome CFC Syndrome medicine.disease Dermatology Osteochondrodysplasia digestive system diseases PTPN11 Phenotype Endocrinology Case-Control Studies Skin Abnormalities ras Proteins Noonan syndrome KRAS business Signal Transduction |
| Zdroj: | American journal of medical genetics. Part A, 143A(8), 799-807. Wiley-Liss Inc. |
| ISSN: | 1552-4825 |
| Popis: | 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 in MAPK3/1 (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. |
| Databáze: | OpenAIRE |
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