Identification of a Novel Missense Mutation in the Sterol 27-Hydroxylase Gene in Two Japanese Patients with Cerebrotendinous Xanthomatosis

Abstract

Abstract

Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing

“…This mutation was confirmed by Sanger sequencing ( Fig. 2B and C ), and it has previously been reported to cause such a condition in other patients ( 9 ).…”

“…Accordingly, when we encounter patients presenting with tendon xanthomas and AAA, we typically suspect them of having FH. However, there are other types of inherited diseases complicated by tendon xanthomas, such as autosomal recessive hypercholesterolemia (ARH), sitosterolemia, and cerebrotendinous xanthomatosis (CTX) ( 7 - 9 ).…”

A Late-onset and Relatively Rapidly Progressive Case of Pure Spinal Form Cerebrotendinous Xanthomatosis with a Novel Mutation in the <i>CYP27A1</i> Gene

“…2B ). The c.1420C>T (p.R474W) is the fourth most common variant in Japanese CTX patients ( 4 , 9 - 11 ), whereas the c.784C>T (p.R262C) variant has not been described in disease-causing mutation databases, such as the Human Gene Mutation Database (HGMD) Professional (http://www.hgmd.org/) and ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/). The possible impact of the novel p.R262C variant on the structure and function of sterol 27-hydroxylase was assessed using bioinformatics tools, including SIFT (https://sift.bii.a-star.edu.sg/), Polyphen2 (http://genetics.bwh.harvard.edu/pph2/), Mutation Tester (http://www.mutationtaster.org/), and CADD (https://cadd.gs.washington.edu/), and it was predicted to be highly deleterious ( Table ).…”

Clinical and Radiological Findings of a Cerebrotendinous Xanthomatosis Patient with a Novel p.A335V Mutation in the <i>CYP27A1</i> Gene

“…Progressive cholestanol deposition induces the formation of juvenile cataracts, tendinous xanthomas, osteoporosis, premature atherosclerosis and neurological symptoms, including psychomotor delays, cognitive impairment, ataxia, pyramidal and extrapyramidal symptoms, epilepsy, peripheral neuropathy and psychiatric disorders (3)(4)(5)(6)(7)(8). To date, over 50 mutations in the CYP27A1 gene have been reported around the world (5,(9)(10)(11)(12)(13)(14). We herein describe the clinical, neuroradiological and molecular biological findings of a Japanese CTX patient with a novel missense mutation in the CYP27A1 gene.…”