Genetic diagnosis of 154 patients with suspected spinal muscular atrophy and its clinical value

Abstract

Objective To explore the clinical value of genetic diagnosis of SMA, the homozygous deletion of survival motor neuron 1 (SMN1) gene in suspected spinal muscular atrophy (SMA) patients were analyzed in this study. Methods A total of 154 patients suspected with SMA and 20 healthy volunteers were recruited from January 2007 to December 2014 in the Genetic Diagnosis Center of the First People′s Hospital of Yunnan Province and the Department of Neurology of the Fourth Affiliated Hospital of Kunming Medical University. Potential deletions in exons 7 and 8 of SMN1 gene were screened by use of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method in both 154 patients suspected with SMA and 20 healthy volunteers. The frequencies of the deletions in exons 7 and 8 of SMN1 were calculated and statistical analysis of different deletion types among 3 SMA groups was performed with SPSS 13.0 software package. Results Among 154 suspected SMA patients, 101 cases with homozygous deletions of exon 7 of SMN1 gene were detected, which accounted 65.6% (101/154) of the suspected SMA patients. Among the 101 SMA patients, 97.0% (98/101) of the patients with both homozygous deletions of exons 7 and 8 for SMN1 gene and 3.0%(3/101) of the patients with homozygous deletions of only exon 7 for SMN1 gene were detected.The patient with only deletion of exon 8 for SMN1 gene was notdetected. Four cases with negative results were subjected to be followed-up, but they were characteristic of SMA symptom by clinical re-visit. Thus, total 105 patients were confirmed with SMA, among them, 68 were type Ⅰ SMA, 27 were type Ⅱ SMA, and 10 were type Ⅲ SMA, which accounted for 64.8%(68/105), 25.7% (27/105) and 9.5% (10/105) of the SMA patients, respectively. Type Ⅳ SMA was not observed in these patients. No deletion was detected among 20 healthy volunteers. Conclusions PCR-RFLP assay is a noninvasive, simple, high sensitive and specific method for SMA diagnosis, which can be considered as the first-line genetic test for the suspected SMA patients. It will help to improve the accuracy of clinical diagnosis and the detection rate by strengthening the clinical diagnostic criteria and re-evaluating the suspected patients after negative genetic diagnosis.(Chin J Lab Med, 2015, 38: 833-837) Key words: Muscular atrophy, spinal; Survival of motor neuron 1 protein; Polymerase chain reaction; Polymorphism, restriction fragment length