Abstract: 【Abstract】 Objective To determine mutations in the PTPN11 gene in a family with LEOPARD syndrome. Methods Clinical evaluation was carried out in a large pedigree with confirmed LEOPARD syndrome diagnosed in Hwa Mei Hospital, University of Chinese Academy of Sciences. Peripheral blood samples were obtained from 4 patients and 2 unaffected healthy members in the family, as well as 100 unrelated healthy controls. DNA was extracted from the blood samples, and PCR was performed to amplify all exons of the PTPN11 genes, followed by Sanger sequencing. Results There were 14 members in 3 generations of the family, 6 of whom were affected （3 males and 3 females）, demonstrating an autosomal dominant inheritance pattern. Skin lesions were mainly distributed on the face, trunk and limbs, accompanied by special facial features and cardiovascular system abnormalities. A missense mutation c.1632G>T （p.R558L） in the PTPN11 gene was identified in the 4 patients, which resulted in the substitution of arginine by leucine at amino acid position 558. This mutation had not yet been reported previously. No mutation was detected in the PTPN11 gene in the 2 unaffected family members or 100 healthy controls. Conclusion The missense mutation c.1632G＞T in exon 13 of the PTPN11 gene may be the molecular basis for LEOPARD syndrome in this family.

Key words: LEOPARD syndrome, DNA mutational analysis, Lentigo, PTPN11 gene