The Molecular Genetics Research On Type A Niemann-Pick Disease

Background and ObjectiveGenetic metabolic disease is a kind of serious disease which do harm to the physical and mental health of human, not only a heavy burden on families and society, but also threaten future generations and improving the quality of a direct impact on the population. Since the majority of the treatment of genetic diseases is still quite costly or difficult to implement universally, therefore, to reduce the incidence of genetic disease, extensive prevention efforts is particularly important. ObjectiveThis study aimed to explore the molecular basis and assess the feasibility of gene diagnosis for the two unrelated Chinese families with Type A Niemann Pick Disease (NPA), and to investigate the genotype-phenotype correlation.MethodsTwo patients and their healthy family members in two unrelated families with Niemann Pick Disease were investigated. Genomic DNA was extracted from peripheral blood sample of each patient and healthy family member. The all 6 coding exons of SMPD1 and some of their flanking intronic sequences were amplified by polymerase chain reaction (PCR), and direct bilateral sequencing of the PCR products was used to identify the possible mutation. The sequencing results were compared and analyzed with the normal sequence of Genebank, and the mutation was further confirmed by sequencing again.Results1. In the first family, bilateral sequencing of PCR amplified fragments in proband revealed a homozygous T to C transition mutation at nucleotide 107 in exon lof SMPD1.The other healthy family members'revealed a heterozygous T to C transition mutation at nucleotide 107 in exon lof SMPD1. These nucleotide changes converted a GTG codon to an GCG codon, which gave rise to amino acid substitutions of valine (Val,V) for alanine(Ala,A) at codon 36 (V36A).It was a missense mutation.2. In the second family, bilateral sequencing of PCR amplified fragments in proband revealed a homozygous T to C transition mutation at nucleotide 107 in exon lof SMPD1.His mother's revealed a heterozygous T to C transition mutation at nucleotide 107 in exon 1of SMPD1. These nucleotide changes converted a GTG codon to an GCG codon, which gave rise to amino acid substitutions of valine(Val,V) for alanine(Ala,A) at codon 36 (V36A).It was a missense mutation.Conclusions1. The SMPD1 gene was responsible for the five unrelated Chinese families with NPD, and it conformed to the prior report.2. The mutations of SMPD1 gene were reported for the first time,and this report further extends the mutation spectrum of this gene.3. The mutations were the molecular basis of 5 unrelated Chinese families with NPD, and the identification of these mutations will facilitate prenatal diagnosis, genetic diagnosis and genetic counseling.