摘要
目的分析NADH脱氢酶（泛醌）黄素蛋白2（NDUFV2）基因突变所致白质脑病一家系兄弟2例患儿的临床及影像学特点，以提高临床医师对本病的认识及对此病的早期识别。方法收集并分析先证者及其家系成员的临床资料，分析其临床症状和头颅磁共振成像（MRI）特点，并对2例患儿进行长期随访。先后采用Saner测序、靶向捕获二代测序、全外显子组基因测序技术对该家系2例患儿及其父母进行遗传学分析。结果1．临床特点及随访：2例患儿分别于出生后4个月和1岁起病，表现为运动功能快速倒退、肌张力增高、病理征阳性，随访过程中病情相对稳定静止或逐渐好转，鸡尾酒疗法后病情有好转。2．头颅MRI特点：以深部白质受累为主，均为脑室周围长T1、长T2、液体衰减反转恢复序列（FLAIR）高信号，病灶呈团块状对称分布，病灶内信号不均匀，均伴囊性改变，弥散加权像（DWI）病灶呈团块状高信号。随访发现急性期后病灶多逐渐好转，但仍保留囊性改变，DWI呈线状或点状高信号，范围较前缩小。3．基因突变分析：先证者及其弟弟NDUFV2基因均存在复合杂合突变：c．467T〉A和c．404G〉C，其中前者遗传自父亲，后者遗传自母亲，均为国际上未报道的新突变。结论本研究报道的2例患儿与国际上已报道的12例患儿肥厚性心肌病合并脑病及Leigh综合征2种表型截然不同，以亚急性起病之后相对静止的白质脑病为临床表型，扩大了NDUF~基因的临床表型谱。明确了该白质脑病家系中的致病基因为NDUFV2基因突变，为该家庭进行准确的遗传咨询提供了可能。
Objective To analyze the clinical and imaging features of 2 siblings with leukoencephalopathy due to NADH dehydrogenase （ubiquinone） flavoprotein 2 （NDUFV2） gene mutation,in order to better understand and diagnose it earlier. Methods Clinical and follow - up data of the proband and his brother were collected. Clinical features including symptoms, signs and cranial magnetic resonance imaging （MRI） were analyzed, and 2 patients were followed up for a long time. Sanger sequencing, targeted next generation sequencing, and whole exome sequencing were performed to identify potential genetic variations in the 2 patients and their parents. Results （ 1 ） Clinical characteristics and follow - up ： ages of onset were 4 months and 1 year respectively. Both of the patients presented rapid motor regression hyperinyotonia, positive pathological character. During the follow - up the condition became stable, motor function and cognition improved gradually after cocktail therapy. （2） Brain MRI of the 2 patients showed prominent abnormalities in deep cerebral white matter, presenting T1 hypointense, T2 and fluid attenuated inversion recovery （FLAIR） hyperin- tense in the periventricular area. FLAIR images revealed that the abnormal white matter was partially rarefied and cavi- tared. Diffusion weighted images （DWI） showed high signals along the periphery of the involved areas. The follow - up MRI showed the cavitation still existed and even expanded, and DWI showed regional linear or spotty high signals around the original lesions. （ 3 ） Novel mutations in NDUFV2 gene, c. 467T 〉 A and c. 404G 〉 C, were identified in proband and his brother. The former inherited from his father,while the latter inherited from his mother,which was the new mutation not reported in the international. Conclusions The clinical features of the brothers presented subacute leukoencephalopathy with relatively stable or improved outcome. This was distinctive from the phenotypic features reported in 12 cases with hypertrop
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2017年第12期920-923,共4页
Chinese Journal of Applied Clinical Pediatrics
