OBJECTIVETo explore the role of sphingomyedlin phosphodiesterase 1 (SMPD1) gene mutations in the pathogenesis of Parkinson's disease (PD).

METHODSFor 110 Chinese patients with PD, all exons of the SMPD1 gene were sequenced, and the results were compared with reference sequence from GenBank to identify possible mutations.

RESULTSA novel heterozygous mutation Ex2:c.677C>A/p.P226Q (likely pathogenic) was identified in a patient, which resulted in substitution of Glutamic acid by Proline at position 226. In addition, two known single nucleotide polymorphisms (SNPs) Ex1:c.107T>C/p.V36A (benign) and Ex6:c.1522G>A/p.G508R (benign), and three previously reported SMPD1 mutations Ex2:c.T371T>G/p.L124R (uncertain significance), Ex2:c.636T>C/P.(=)(benign) and Ex6:c.1598C>T/p.P533L (uncertain significance) were identified. The novel p.P226Q mutation and p.P533L mutation were predicted to have a possibly damaging effect on the structure and function of SMPD1 protein, which in turn may lead to PD.

CONCLUSIONThe mutation rate of the SMPD1 gene was 3.64% among Chinese PD patients. Genetic variants of SMPD1 may increase the risk of PD.