Molecular Genetics of LEOPARD Syndrome

Abstract

LEOPARD syndrome (LS) is an acronym for the cardinal features lentigines, electrocardiogram conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensor ineural deafness. However, other disorders, such as hyper trophic cardiomyopathy, occur frequently and represent a potentially life-threatening problem. PTPN11 mutations, located on chromosome 12q24, are observed in up to 90% of patients with LS.Meanwhile,mutations in the RAF1 gene on chromosome 3p25.2 and mutations in the BRAF gene on chromosome 7q34 occur in 5% of the cases. Eleven differ ent missense PTPN11 mutations, characterised by a decrease in physiological activity of the mutated protein (Tyr279Cys/Ser, Ala461Thr, Gly464Ala, Thr468Met/Pro, Arg498Trp/Leu, Gln506Pro and Gln510Glu/Pro) have been reported, two of which (Tyr279Cys and Thr468Met) occur in approximately 65% of the cases.