Department of Neurology & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China.
Department of Neurology, Jing'an District Center Hospital of Shanghai, 259 Xikang Road, Shanghai, 20040, China.
Metab Brain Dis. 2017 Oct;32(5):1609-1618. doi: 10.1007/s11011-017-0047-8. Epub 2017 Jun 17.
Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations in CYP27A1. 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) in CYP27A1 were 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 in CYP27A1. 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.
脑腱性黄瘤病（CTX）是一种由 CYP27A1 基因突变引起的脂质贮积病。目前中国 CTX 的文献主要基于病例报告。本研究旨在调查中国 CTX 患者的临床表现和遗传特征。收集了 4 个中国 CTX 家系的临床资料，采用聚合酶链反应加 Sanger 测序进行基因检测，并对以往报道的中国 CTX 患者的特征进行了复习。在 CYP27A1 中发现了三个新的突变，分别为家系 1 的 p.Arg513Cys、c.1477-2A>G 和家系 4 的 p.Arg188Stop（NM_000784.3）。本研究中的先证者在家族 1 和 4 中表现为小脑共济失调、腱黄瘤和痉挛性轻瘫，在家族 2 中表现为腱黄瘤伴痉挛性截瘫，在家族 3 中表现为无症状腱黄瘤。在家族 2、3 和 4 中分别发现了三个已知的突变，分别为 p.Arg137Gln、p.Arg127Trp 和 p.Arg405Gln。在回顾的中国患者中，最常见的发现是黄瘤（100%）、锥体束征（100%）、小脑共济失调（66.7%）、认知障碍（66.7%）、白内障（50.0%）和周围神经病（33.3%）。慢性腹泻少见（5.6%）。未发现与任何特定临床特征相关的突变。本研究在 CYP27A1 中发现了 3 个新突变。在中国 CTX 患者中，黄瘤是最常见的症状，而白内障和慢性腹泻较少见。中国 CTX 患者的特殊表现可能是由于缺乏血清胆甾醇检测，需要在未来更大数量的患者中进一步证实。
