Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence

• Published in: European journal of medical genetics Vol. 52; no. 5; pp. 337 - 340
• Main Authors: Koudova, Monika, Seemanova, Eva, Zenker, Martin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Masson SAS 01.09.2009; Elsevier
• Subjects: Abnormalities, Multiple - genetics; Adolescent; Amino Acid Sequence; Amino Acid Substitution; Biological and medical sciences; BRAF; Cardio-facio-cutaneous syndrome; Complex syndromes; Conserved Sequence; Diseases of the osteoarticular system; DNA - genetics; DNA - isolation & purification; DNA Mutational Analysis; Facies; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Heart Defects, Congenital - genetics; Humans; LEOPARD syndrome; LEOPARD Syndrome - genetics; Leucine - metabolism; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical Education; Medical genetics; Medical sciences; Mitogen-activated protein kinases; Molecular Sequence Data; Mutation; Noonan syndrome; Noonan Syndrome - genetics; Proto-Oncogene Proteins B-raf - genetics; Sequence Homology, Amino Acid; BRAF; LEOPARD syndrome; Cardio-facio-cutaneous syndrome; Noonan syndrome; Mitogen-activated protein kinases; Human; Skin disease; Nervous system diseases; Intelligence; Cardio facio cutaneous syndrome; Enzyme; Transferases; Diseases of the osteoarticular system; Mitogen-activated protein kinase; Cardiovascular disease; Patient; Genetic disease; Genital diseases; ENT disease; Genetics; Mutation; Osteochondrodysplasia
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2009.04.006

Abstract Noonan syndrome (NS) and related disorders are caused by mutations in various genes encoding molecules involved in the RAS–MAPK signalling cascade. There are strong genotype–phenotype correlations. BRAF is the major gene for cardio-facio-cutaneous syndrome (CFCS), and usually patients with a BRAF mutation have significant cognitive impairment. We report on a patient with LEOPARD syndrome and normal intelligence who was found to carry a novel sequence change in BRAF . The mutation p.L245F was demonstrated to be de novo with no evidence of somatic mosaicism. This observation illustrates that the phenotypic spectrum caused by BRAF mutations is broader than previously assumed and that mental retardation is not necessarily associated. We speculate that the impact of p.L245F on BRAF protein function differs either qualitatively or quantitatively from those mutations associated with CFCS.