Pedigree analysis of DYNC1H1 p. P776L mutation in a family with spinal muscular atrophy
10.3760/cma.j.issn.1006-7876.2018.12.003
- VernacularTitle:DYNC1H1基因p.P776L突变致常染色体显性遗传脊肌萎缩症一家系分析
- Author:
Xiaojuan WANG
1
;
Haichang MA
;
Hongzhi GUAN
;
Xiwen GENG
;
Shujian LI
;
Yingying SHI
;
Huiqin LIU
;
Lingzhi QIN
;
Gang LIU
;
Wei LI
Author Information
1. 河南省人民医院神经内科
- Keywords:
DYNC1H1 gene;
Autosomal dominant;
Muscular disorders,atrophic
- From:
Chinese Journal of Neurology
2018;51(12):949-954
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the clinical and electrophysiological features in a family with spinal muscular atrophy (SMA), and assess the probable causative gene mutations for the family. Methods To identify the nosogenesis of the proband with weakness and atrophy in the double lower proximal limbs, clinical data of his 12 family members were collected, and the proband and his mother were selected for clinical examinations, including laboratory tests, electromyogram (EMG), F-wave, H-reflex, X-ray of the spine and double lower limbs, brain and spinal cord magnetic resonance imaging, etc. Moreover, human whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics (ACMG) and the Association for Molecular Pathology (AMP). Subsequently, the strong pathogenic mutation was validated by Sanger sequencing. Results Familial investigation showed seven of 12 family members presented with weakness in the double lower proximal limbs. Among them, three had the main manifestation of atrophy in the double lower proximal limbs, one had high arched foot as the main presentation, and the others had weakness in the double lower proximal limbs. EMG studies showed the abnormal results in the anterior horn of the spinal cord. The strong pathogenic mutation in DYNC1H1 gene (exon8, c.2327C＞T, p.P776L) was identified from the proband according to ACMG and AMP guidelines. Sanger sequencing revealed six patients had this variant and it was passed mainly from his maternal grandmother. Conclusions A pathogenic mutation of the DYNC1H1 p.P776L in six Chinese pedigrees which cosegregated with SMA was identified. There existed individual differences in clinical presentations. This finding may have important implications for the study of SMA in Chinese patients.
