Molecular Analysis Of Genes In5q13Region In Patients With Spinal Muscular Atrophy

Objectives:1. Spinal muscular atrophy (SMA) is a common recessive neuromuscular disease,which is caused by mutations of the survival motor neuron1(SMN1) gene.Additionally, the phenotype is modified by several genes nearby SMN1in the5q13region. In this study, we analyzed the correlation between genes variants in5q13region and disease phenotype in Chinese patients with spinal muscular atrophy.2. Because SMA is incurable, carrier testing and prenatal diagnosis play animportant part in disease prevention. Here, we tried to initiate a preliminary study ofcarrier testing and prenatal diagnosis of spinal muscular atrophy.Methods:1. We adopted PCR-RFLP, sequencing, MLPA and QMPSF to analyze thecorrelation between genes variants and the SMA phenotype in157Chinese patients.2. We analyzed the SMN1variants of SMA carrier and carrier frequency of SMAby MLPA technique, and adopted amniotic cell culture, PCR-RFLP and MLPA toperform prenatal diagnosis of SMA pedigree.Results:1. Most patients (94.90%) possessed a homozygous SMN1deletion, while10patients demonstrated only the absence of exon7, but the presence of exon8.2. Two novel subtle mutation (c.689C>T and c.844C>T) were identified in2patients who both carried a single copy of SMN1.3. There were inverse correlations between SMN2, the NAIP copy number, andthe clinical severity of the disease.4. Seven type I patients possessed large-scale deletions, including SMN1, NAIP,GTF2H2and H4F5.5. Most (89.26%) SMA carrier possessed one copy of SMN1, and the carrier frequency of Fujian Province was1in32.6. By the way of prenatal diagnosis, it is found that3fetus of15SMA pedigreeis a SMA patient.Conclusions：1. SMN1subtle mutations, SMN2copy number, and the extent of deletion in the5q13region should all be considered in the genotype-phenotype analysis of SMA.2. As most SMA carrier possessed one copy of SMN1, it is feasible to screen outthe carriers by analyzing the copy number of SMN1.3. SMA carrier testing and prenatal diagnosis play an important part in diseaseprevention.