Niemann-Pick disease (NPD) results from the deficiency of lysosomal acid sphingomyelinase (SMPD1). To date, out of more than 70-disease associated alleles only a few of them have a significant frequency in various ethnic groups. In contrast, the remainder of the mutations are rare or private. In this paper we report the molecular characterization of an Italian series consisting of twenty-five NPD patients with the severe neurodegenerative A phenotype. Mutation detection identified a total of nineteen different mutations, including 14 novel mutations and five previously reported lesions. The known p.P189fs and the novel p.T542fs were the most frequent mutations accounting for 34% and 18% of the alleles, respectively. Screening the alleles for the three common polymorphisms revealed the variant c.1516G>A (exon 6) and the repeat in exon 1, but not the variant c.965C>T (exon 2). In absence of frequent mutations, the prognostic value of genotyping is limited. However, new genotype/phenotype correlations were observed for this disorder that could in the future facilitate genetic counseling and guide selection of patients for therapy.
Copyright 2004 Wiley-Liss, Inc.