Background & Aims: Niemann-Pick disease (NPD) types A and B are rare autosomal recessive disorders that occur due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, which result in the deficiency or shortage of lysosomal acid sphingomyelinase (ASM) activity. The disorder is characterized by the accumulation of sphingomyelin in the endolysosomal sections, and patients often present with hepatosplenomegaly, atherogenic lipid profiles, respiratory complications, and sometimes progressive neurodegeneration.

Materials & Methods: In this study, we report the molecular characterization of seven unrelated Iranian Azeri Turk patients with types A and B NPD by sequencing SMPD1 exons. For collecting more information about the frequency of the polymorphic hexanucleotide sequence, P.37LA (3-8), residing within the signal peptide of ASM, we also designed a control group consisting of 50 healthy participants with the same ethnic background.

Results: L137P missense mutation was observed in three of the seven patients in a homozygous state. Four patients were homozygous for rs1050239. In the case of P.37LA (3-8), the allele contained four hexanucleotide repeat units, the most frequent in both patients and healthy participants, followed by five, six, and seven repeats. However, five repeats were found for both cases in the ENSEMBLE and UCSC databases, whereas in the NCBI database, seven repeats are considered as a common allele.

Conclusion: L137P was the only pathogenic mutation found in this investigation. The existence of an allele with four repetitions with a high frequency for P.37LA (3-8) in our population can be an example of the founder effect.

SOURCE: URMIA MED J 2016: 26(12): 1053 ISSN: 1027-3727