Clinical and genetic characteristics of spinal muscular atrophy with SMN1 gene compound heterozygous mutations in 3 pedigrees
10.3760/cma.j.cn113694-20240826-00581
- VernacularTitle:SMN1基因复合杂合变异所致脊髓性肌萎缩3个家系的临床特征及遗传学分析
- Author:
Gang LI
1
;
Jun FU
;
Mi PANG
;
Jia SONG
;
Mingming MA
;
Jiewen ZHANG
Author Information
1. 河南省人民医院（郑州大学人民医院）神经内科，郑州 450003
- Publication Type:Journal Article
- Keywords:
Muscular atrophy, spinal;
Point mutation;
Loss of heterozygosity;
SMN1 gene
- From:
Chinese Journal of Neurology
2025;58(2):147-153
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.
