Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence.
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.
Koudova
Monika
M
Institute of Biology and Medical Genetics, Charles University, University Hospital Prague, Prague, Czech Republic.
Seemanova
Eva
E
Zenker
Martin
M
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D019066:Facies; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D044542:LEOPARD Syndrome / Q000235:genetics*; D007930:Leucine / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009634:Noonan Syndrome / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D004247:DNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D007930:Leucine