Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families
Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families
复制标题
中国家系脑腱黄瘤病患者的临床及分子遗传学特征
DOI：
10.1007/s11011-017-0047-8
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发表时间：
2017-10-01
影响因子：
3.6
通讯作者：
Ding, Zheng-Tong
中科院分区：
文献类型：
--
作者：
Chen, Chen;Zhang, Yue;Ding, Zheng-Tong
脑腱黄瘤病 (CTX) 是一种由 CYP27A1 突变引起的脂质储存疾病。目前中国CTX的发表主要以病例报告为主。在这里，我们调查了中国 CTX 患者的临床表现、遗传特征。收集4个中国CTX家系的临床资料。基因检测通过聚合酶链反应加桑格测序完成。还回顾了之前报道的中国 CTX 患者的特征。在 CYP27A1 中发现了三个新突变：家族 1 中的 p.Arg513Cys、c.1477-2A > C 和家族 4 中的 p.Arg188Stop (NM 000784.3)。本研究的先证者在家系1和家系4中表现为小脑性共济失调、肌腱黄色瘤和痉挛性轻瘫，在家系2中表现为肌腱黄色瘤加痉挛性截瘫，在家系3中表现为无症状肌腱黄色瘤。家系2、3和3中分别发现了p.Arg137Gln、p.Arg127Trp和p.Arg405Gln 3个已知突变。 4. 对于所审查的中国患者，最常见的表现是黄瘤病（100%）、锥体征（100%）、小脑性共济失调（66.7%）、认知障碍（66.7%）、白内障（50.0%）和周围神经病变（33.3%）。慢性腹泻并不常见（5.6%）。没有发现与任何给定临床特征相关的突变。我们在 CYP27A1 中发现了 3 个新突变。在中国 CTX 患者中，黄瘤病是最常见的症状，而白内障和慢性腹泻则较少见。中国CTX患者的特殊特征可能是由于缺乏血清胆甾醇检测所致，未来应在更多患者中得到证实。
Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations inCYP27A1. Current publications of Chinese CTX were mainly based on case reports. Here we investigated the clinical manifestations, genetic features in Chinese CTX patients. The clinical materials of 4 Chinese CTX pedigrees were collected. The genetic testing was done by polymerase chain reaction plus Sanger sequencing. The features of Chinese CTX patients reported previously were also reviewed. Three novel mutations of p.Arg513Cys, c.1477-2A > C in family 1 and p.Arg188Stop in family 4 (NM 000784.3) inCYP27A1were found. The probands in our study manifested cerebellar ataxia, tendon xanthoma and spastic paresis in family 1 and 4, tendon xanthoma plus spastic paraparesis in family 2, asymptomatic tendon xanthoma in family 3. Three known mutations of p.Arg137Gln, p.Arg127Trp and p.Arg405Gln were found respectively in Family 2, 3 and 4. For the Chinese patients reviewed, the most common findings were xanthomatosis (100%), pyramidal signs (100%), cerebellar ataxia (66.7%), cognitive impairment (66.7%), cataracts (50.0%), and peripheral neuropathy (33.3%). Chronic diarrhea was infrequently seen (5.6%). No mutation was found associated with any given clinical features. We identified 3 novel mutations inCYP27A1.In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. The special features in Chinese CTX patients might caused by the lack of serum cholestanol test and should be confirmed in larger number of patients in the future.