Clinical and genetic analysis of a case of spastic paraplegia type 76 caused by CAPN1 gene mutation
10.3760/cma.j.cn113694-20240918-00625
- VernacularTitle:CAPN1基因变异所致76型痉挛性截瘫1例的临床及遗传学分析
- Author:
Yan LIU
1
;
Lanqing LIU
;
Yanting LI
;
Qiying SUN
Author Information
1. 中南大学湘雅医院神经内科，长沙 410008
- Publication Type:Journal Article
- Keywords:
Spastic paraplegia, hereditary;
CAPN1 gene;
Hereditary spastic paraplegia type 76
- From:
Chinese Journal of Neurology
2025;58(6):640-649
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To report a case of spastic paraplegia type 76 (SPG76) caused by a novel mutation of the CAPN1 gene, and collect the SPG76 cases published in recent years to summarize the clinical phenotype and genetic characteristics and improve the understanding of this disease. Methods:The clinical data of a patient with SPG76 caused by a mutation of the CAPN1 gene were collected, who admitted to Xiangya Hospital of Central South University on April 22, 2024. Relevant literature was searched in PubMed and China National Knowledge Infrastructure databases using the search terms "hereditary spastic paraplegia 76" "spastic paraplegia type 76" "SPG76" and a literature review was performed. Results:The patient was a 44-year-old male with the main symptoms of unsteady walking. Physical examination showed spasticity of both lower limbs, increased muscle tension of the limbs, hyperreflexia of the tendons. Brain and spinal cord magnetic resonance imaging showed no significant abnormalities. Neuroelectrophysiological examination showed no abnormalities in nerve conduction study and needle electromyography, and high amplitude F-waves were observed in the bilateral median nerves. Whole exome sequencing showed that there were compound heterozygous mutations of the CAPN1 gene: c.759+1G>A and c.1341+2T>G, of which c.1341+2T>G had not been reported. A total of 80 SPG76 cases related to CAPN1 gene mutations were reported in the literature, with an average age of onset of 25.68 years, and the clinical manifestations were mainly bilateral lower limb spasticity and tendon hyperreflexia, and about half of the patients were accompanied by upper limb spasticity and tendon hyperreflexia, ataxia, dysarthria, or lower limb weakness. Magnetic resonance imaging of the brain and spinal cord was mostly normal, and 13.8% (11/80) of the patients showed varying degrees of changes in the brain, mainly involving the cerebellum, and 5.0% (4/80) of the patients had cervical and thoracic spinal cord atrophy. The mutation types of CAPN1 gene included missense, nonsense, frameshift, and splice site variation, and the mutation sites were scattered and had no special aggregation tendency, and a total of 14 patients from 9 families carried the c.1176 G>A mutation. Conclusions:SPG76 is a rare subtype of hereditary spastic paraplegia caused by CAPN1 gene mutation, which is more common in young and middle-aged people, and patients have spasticity and tendon hyperreflexia in both lower limbs as the main clinical manifestations, most of which are accompanied by changes in the upper limbs, ataxia, etc., and a small number of patients can show atrophy of the cerebellum and (or) cervical and thoracic spinal cord by magnetic resonance of the head and spinal cord. The CAPN1 gene variants mainly include missense and nonsense variants, and c.1176G>A variant is the most prevalent pathogenic mutation site in the CAPN1 gene.
