AUTHOR=Guoliang You , Zhaoxia Wang , Lin Zhang , Xuan Chen , Xiaodong Zhang , Xiaolian Xing , Yangli Su , Tianli Zhang , Yanping Zhu , Jiangping Wang , Qing Liu 

TITLE=Clinical and genetic analysis of a family with cerebrotendinous xanthomatosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1566740

DOI=10.3389/fneur.2025.1566740

ISSN=1664-2295

ABSTRACT=ObjectiveThis study aims to analyze the clinical and genetic characteristics of cerebrotendinous xanthomatosis (CTX) in a Chinese family.MethodsClinical data, including medical history, neurologic and auxiliary examinations, imaging studies, and genetic profiles were collected from a Chinese CTX family at Taiyuan City Central Hospital. The proband underwent whole exome sequencing, which was confirmed via Sanger sequencing in two affected and five unaffected family members.ResultsTwo patients in the pedigree exhibited compound heterozygous missense variants in the CYP27A1 gene: c.379C > T, (pathogenic variants) and c.397 T > C, (a variant of uncertain clinical significance), both located in exon 2. A literature review revealed that c.1263 + 1G > A and C.379C > T are the most common variants in genetically diagnosed Chinese CTX patients, with exon 2 of the CYP27A1 gene.ConclusionThe compound heterozygous variants c.379C > T (p. Arg127Trp) and c.397 T > C (p. Trp133Arg) in the CYP27A1 gene are likely the cause of CTX in this pedigree. This finding expands our understanding of the genetic and clinical spectrum of CTX and provides significant insights for its diagnosis.