脊髓小脑性共济失调1型一家系谱分析

Clinical and molecular biological study on a Chinese family of spinocerebellar ataxia type 1

目的探讨分子基因学及临床特点对脊髓小脑共济失调1型(spinocerebellar ataxia type1,SCA1)家系诊断的临床意义。方法采集一SCA1患者家系共8人,其中4例为临床症状阳性患者,4人为无临床症状者,分析患者家系成员的临床表现、影像学及电生理检查结果特点,采用PCR-STR分析法对8位家系成员进行ATXN1基因CAG序列检测。结果该家系中8人均存在ATXN1基因CAG序列异常扩增。4例患者首发症状均为小脑共济失调,主要表现进行性步态不稳,并伴有构音障碍、饮水呛咳、双眼上视不充分。MRI检查结果示小脑萎缩。神经电生理检查显示不同程度的异常,4例临床症状阳性患者尤为突出。结论 SCA1临床表现为进展性的小脑共济失调及脑干功能损害,临床症状阳性结合基因检测可诊断。

Objective To investigate the clinical and molecular biological features of spinocerebellar ataxia type1(SCA1).Methods A total of 8 members of a SCA1 family were tested,of which 4 people were clinical positive patients and the rest were asymptomatic.The clinical manifestations,imaging and electrophysiological findings of the family members were analyzed.PCR-STR was used to detect the abnormal CAG trinucleotide expansion in ATXN1. Results The abnormal CAG trinucleotide expansion in ATXN1 were detected in the 8 people.The initial manifestation of the 4 patients were progressive cerebellar ataxia,mainly manifested as gait disturbance,difficulty in walking and accompanied with dysarthria,dysphagia and up-gaze palsy.Neuropathological studies revealed cerebellum and brain stem atrophy.Neuroelectrophysiological examination showed different degrees of abnormalities,especially in the 4 patients with positive clinical symptoms.Conclusions SCA1 is inherited in an autosomal dominant manner.Progressive cerebellar ataxia and bulbar dysfunction are common.The diagnosis of SCA1 rests on the result of molecular genetic testing and clinical characteristics.