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目的 分析转甲状腺素蛋白(TTR)突变所致的眼软脑膜淀粉样病(OLMA)一家系的临床、影像和基因学特征.方法 收集1例于2015年9月25日就诊于唐都医院,由TTR基因Leu 12Pro突变导致的OLMA患者的家系资料以及外周血标本,首先对先证者进行全外显子检测,并对其父亲、姐姐等进行家系验证.分析该病临床、神经影像学及基因学特点.结果 本例OLMA患者主要以短暂性脑缺血发作为表现,其他临床表现包括头痛、全身乏力、自主神经功能障碍和视力、听力、记忆力下降.头颅核磁共振可见软脑膜、脊膜强化,腰椎穿刺提示脑脊液蛋白明显升高,眼科检查提示双侧瞳孔扩大,对光反应迟钝,有干眼征、玻璃体混浊、轻度白内障.基因检测提示:先证者、先证者姐姐、姐姐大女儿和先证者大儿子TTR基因2号外显子c.95T＞C Leu12Pro突变.结论 如果患者存在中枢神经系统症状且伴有以下表现,如家族史、自主神经功能障碍、心脏病、听力或视力受累,同时头颅核磁共振增强扫描可见软脑膜强化、脑脊液蛋白增高,应警惕该病可能,基因检测有助于该疾病诊断.

Objective To discuss the characteristics of clinical presentation,neuroimaging and genetics in a Chinese family of oculeptomeningeal amyloidosis (OLMA) associated with the transthyretin (TTR) Leul2Pro mutation.Methods Clinical characteristics of the pedigree and peripheral blood samples of an OLMA patient with TTR Leu12Pro mutation were collected from Tangdu Hospital on September 25,2015.Firstly,exon detection was performed on the proband and the family validation of her father and sister was carried out.The clinical,neuroimaging and genetic characteristics of the disease were analyzed.Results A 36-year-old right-handed woman was suffered recurrent episodes of slurred speech with right-sided weakness.She presented initi.ally with headache,autonomic dysfunction,visual and hearing loss.Magnetic resonance imaging showed extensive leptomeningeal enhancement,and cerebrospinal fluid analysis showed a raised protein of 1566.54 mg/L.The examination of the both eyes showed dry eye,vitreous opacity,and mild cataract.The proband and her sister,the sister's eldest daughter,the proband's son showed c.95T＞C mutation in exon2 of TTR gene and Leu12Pro mutation in TTR protein.Conclusions OLMA should be suspected if central nervous system symptoms are observed in combination with one or more of the following:family history of a neuropathy,autonomic dysfunction,cardiac hypertrophy,hear or ocular involvement,gadolinium-enhanced magnetic resonance imaging of the brain and spine revealing diffuse leptomeningeal enhancement,lumbar puncture demonstrating elevated protein without evidence of malignant cells on cytology.Genetic testing for pathogenic mutation in TTR gene is helpful for diagnosis of OLMA.