ORIGINAL ARTICLE Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families Chen Chen 1 & Yue Zhang 1 & Hui Wu 2 & Yi-Min Sun 1,4 & Ye-Hua Cai 3 & Jian-Jun Wu 1 & Jian Wang 1 & Ling-Yun Gong 1,4 & Zheng-Tong Ding 1 Received: 10 March 2017 /Accepted: 1 June 2017 # Springer Science+Business Media, LLC 2017 Abstract Cerebrotendinous xanthomatosis (CTX) is a lipid- storage disease caused by mutations in CYP27A1. Current publications of Chinese CTX were mainly based on case re- ports. 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 sequenc- ing. 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 spas- tic 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 fea- tures. We identified 3 novel mutations in CYP27A1. In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less fre- quent. 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. Keywords Cerebrotendinous xanthomatosis . CYP27A1 . Mutations . Clinical features . Chinese Introductions Cerebrotendinous xanthomatosis (CTX) is a rare autosomal- recessive inborn disorder of bile acid metabolism due to mu- tations in the CYP27A1 gene (OMIM *606530) on chromo- some 2q35 (Bjorkhem 2013). The CYP27A1 gene has 9 exons, encodes the mitochondrial enzyme sterol 27-hydroxy- lase, which is an important enzyme in Bclassic and alternative pathways ^ of bile acid synthesis (Lorbek et al. 2012; (Schimschock et al. 1968; (Vogeli et al. 2013). CTX has diverse clinical manifestations. Classical symp- toms includes childhood chronic diarrhea, juvenile bilateral cataracts, psychomotor retardation, tendon xanthomas, pro- gressive dementia with cerebello-pyramidal signs, osteoporo- sis and premature atherosclerosis (Federico and Dotti 2003). Elevated levels of cholestanol levels in serum, high bile alco- hol levels in urine and plasma, cranial magnetic resonance Chen Chen, Yue Zhang and Hui Wu contributed equally to the work Electronic supplementary material The online version of this article (doi:10.1007/s11011-017-0047-8) contains supplementary material, which is available to authorized users. * Ling-Yun Gong glytt2008@126.com * Zheng-Tong Ding zhtding@hotmail.com 1 Department of Neurology & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China 2 Department of Neurology, Jing’an District Center Hospital of Shanghai, 259 Xikang Road, Shanghai 20040, China 3 Ultrasound Department, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China 4 Department of Neurology, Huashan Hospital North, 108 Luxiang Road, Shanghai 201907, China Metab Brain Dis DOI 10.1007/s11011-017-0047-8