OBJECTIVETo assess the association of copy number variations of SMN1, SMN2, NAIP, GTF2H2 and H4F5 genes with clinical classification of spinal muscular atrophy in children, and determine the copy number of the SMN gene among pregnant women. A carrier screening was also performed in Sichuan province.

METHODSThe copy number variations of the above genes among 53 confirmed SMA patients were determined with MLPA technique. The copy number variations were analyzed by the Fisher's exact test. Deletion of exon 7 in the SMN1 gene was screened with denaturing high performance liquid chromatography (DHPLC) for 427 pregnant women.

RESULTSAmong the 53 cases of type I, II, and III SMA patients, the rate of homozygous deletion of both exons 7 and 8 of the SMN1 gene were 100%, 94.44% and 87.50%, respectively, whereas those of homozygous deletion of exon 7 of SMN1 gene were 0, 5.56%, and 12.50%, respectively. The patients with 1, 2, 3, and 4 copies of exon 7 of the SMN2 gene were 11.32%, 67.92%, 13.21% and 7.55%, respectively. The patients with 0, 1, and 2 copies of exon 5 of NAIP gene were 11.32%, 62.26%, and 26.42%, respectively. No deletion was detected in GTF2H2 or H4F5 genes. The heterozygous loss rate of exon 7 in SMN gene in the pregnant women population of Sichuan region was approximately 2.11%.

CONCLUSIONCopy number variations of SMN2 and NAIP genes in patients are related to SMA clinical types (P < 0.05). In contrast, there was no relationship between SMA clinical types and deletion of exons 7 and 8 in the SMN1 gene (P > 0.05). Analysis of copy number change in SMN1 gene can assist SMA carrier screening. However, when the general population without SMA family history is screened for disease-causing genes, it should be noted that the type "2+0" carriers may affect the screening result, and the result should be interpreted with caution.