SPHINGOMYELINASE GENE MUTATION COMMON IN PATIENTS WITH TYPE A AND B NIEMANN PICK DISEASE IN NORTH WEST, IRAN

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