摘要
目的探讨一个甲状腺运载蛋白(TTR)Val30Ala 突变所致家族性淀粉样多神经病(FAP)家系的临床、病理和分子遗传学特点。方法回顾一个多发性感觉运动神经病家系,共4代27人的临床表现,并对其中2例先证者行电生理检查及腓肠神经活检;对部分患者及健康家属的TFR 基因以 PCR 方法扩增后进行测序。结果发病年龄31～36岁,呈慢性进展性病程,首发症状为双下肢开始的四肢无力、麻木、疼痛,同时或随后出现自主神经功能障碍,消化道症状较为突出。可有心脏受累,表现为肥厚性心肌病,严重的心律失常和直立性低血压。病程后期有耳聋、声音嘶哑等脑神经损害。电生理检查显示周围神经传导测定无波形引出。腓肠神经活检显示有髓纤维几乎全部消失,HE 染色可见神经内膜毛细血管周围均匀粉染的物质,刚果红染色阳性,电镜下为直径7～10 nm不分支的细丝。对 TTR 基因检测,证实外显子2存在 T1099C突变,导致 TTR Val30Ala 突变。结论国内存在 TFR 基因 Val30Ala 突变导致的 FAP 家系,符合Ⅰ型 FAP 的临床表现,除周围神经临床症状外,尚有消化道、心血管和脑神经损害。
Objective To report clinical, pathological and genetic features of familial amyloid polyneuropthy （FAP） associated with TTR Val30Ala mutation in a family in China. Methods Twentyseven members from 4 generations of the FAP family were investigated clinically. Two probands underwent sural biopsy and electrophysiological study. The PCR products of all the 4 TTR exons from the family members were analyzed by direct sequencing. Results The age of onset was between 31 and 36 years. The disease manifested slowly progressing polyneuropathies. The initial symptoms usually included weakness, numbness, paresthesias, and sometimes pain in the feet and lower legs. Extensive autonomic symptoms appeared simultaneously or subsequently. Hypertrophic myocarditis, arrhythmia, orthostatic hypotension and cardiac shock also developed. Cranial nerve involvement （loss of hearing and hoarseness） occurred as a late manifestation in one proband. Nerve conduction velocity could not obtained in electrophysiological examination. Sural nerve biopsy showed amorphous eosinopbilic material on HE staining, which appeared positive on cogon red staining in the endoneurium around capillaries. Myelinated fibers were almost diminished. Electron microscopy showed extracellular amyloid fibrillar deposits composed of 7 - 10 nm wide straight, unbranched fibrils irregularly arranged. DNA analysis of the TTR gene revealed a point mutation T1099C, which was responsible for the substitution of Val for Ala at position 30 of the TTR molecule. Conclusions This is the first TTR Val30Ala induced FAP in China. The clinical presentations can be classified into FAP type Ⅰ . Besides peripheral nerve involvement, gastrointestinal , cardiovascular and cranial nerve impairment are also present.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第3期173-176,共4页
Chinese Journal of Neurology
