RESUMO
Objectives To study the molecular genetics of Niemann-Pick's disease (NPD), and its implication in the diagnosis of NPD. Methods The clinical data and blood samples of three unrelated families were collected. The genomic DNA was extracted from peripheral blood. The six coding exons and their lfanking intronic sequences of SMPD1 gene in all members of three pedigrees were ampliifed by polymerase chain reaction (PCR). The SMPD1 gene sequencing results were compared with the normal sequence from Genbank to identify possible causative mutations. The ampliifcation products of exons where mutations were located were cloned into TA vector for further conifrmation. Results Family 1 proband had homozygous T107C mutation and the parents had heterozygous T107C mutation. The homozygous delete mutation (c.108-113delGCTGGC) was detected and conifrmed by TA cloning in all members of family 2 and 3. The 20 normal control members did not have this delete mutation. Conclusions The genetic basis of NPD in the proband of family 1 is the homozygous T107C mutation in SMPD1 gene, while parents in family 1 are carriers of recessive T107C mutation. The homozygous mutation c.108-113delGCTGGC exists in SMPD1 gene in all members of the family 2 and 3. This delete mutation is considered to be genetic polymorphism.