Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis
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(2019) 14:282
RESEARCH
Open Access
Clinical and genetic characteristics of Chinese patients with cerebrotendinous xanthomatosis Qing-Qing Tao†, Yun Zhang†, Hui-Xia Lin, Hai-Lin Dong, Wang Ni and Zhi-Ying Wu*
Abstract Background: Cerebrotendinous xanthomatosis (CTX) is a rare inborn lipid-storage disease caused by mutations in the sterol 27-hydroxylase (CYP27A1) gene with an autosomal recessive pattern of inheritance. To date, only 19 CTX patients from 16 families have been reported in the Chinese population. Results: Three novel likely pathogenic mutations (c.368_374delCCAGTAC, c.389 T > A and c.571C > T) and 7 previously reported pathogenic mutations (c.379C > T, c.435G > T, c.1016C > T, c.1214G > A, c.1263 + 1G > A, c.1420C > T and c.1435C > T) were identified. In addition, we summarized the genotypes and phenotypes of reported Chinese CTX patients. The most predominant mutations in CYP27A1 were c.410G > A and c.379C > T, and the most common clinical manifestations were pyramidal signs, xanthomatosis, cerebellar ataxia, and cognitive impairment. Conclusion: Our study broadens the genetic and clinical spectrum of CTX and provides insightful information to help better diagnose and understand the disease. Keywords: Cerebrotendinous xanthomatosis, CYP27A1, Mutation, Clinical feature
Introduction Cerebrotendinous xanthomatosis (CTX) (OMIM: 213700) is a rare inborn lipid-storage disease, characterized by accumulation of cholestanol-containing xanthomas predominantly in tendons and the brain [1]. CTX is caused by mutations in the sterol 27hydroxylase gene (CYP27A1) [2]. The human CYP27A1 gene is located on chromosome 2 and contains 9 exons and encodes sterol 27-hydroxylase. Sterol 27-hydroxylase is a mitochondrial cytochrome P450 enzyme that plays a critical role in side-chain oxidation of cholesterol necessary for the synthesis of the bile acid [3–5]. The ability to convert cholesterol
* Correspondence: [email protected] † Qing-Qing Tao and Yun Zhang contributed equally to this work. Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, People’s Republic of China
to bile acids is impaired in CTX patients, leading to the elevations of cholestanol and accumulation of cholesterol and cholestanol in multiple tissues, such as tendons, the central nervous system and lungs [6– 8]. The common clinical presentations include infantile-onset chronic diarrhea, juvenile cataracts, progressive cognitive dysfunction and dementia, cerebellar ataxia, spasticity, osteoporosis, peripheral polyneuropathy and other atypical neurological symptoms [9–12]. However, the clinical manifestations of CTX can vary significantly even within the same family [13]. To date, over 100 variants in the CYP27A1 gene and more than 300 CTX patients have been identified worldwide [14, 15]. In the Chinese population, only 19 patients from 16 families have been reported [16– 27]. Here, we
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