RESUMEN
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disease caused by mutation of CYP27A1 gene. This article reported three cases with clinical phenotypes of CTX and CYP27A1 gene mutation and analyzed the pedigree with a literature review. All the three CTX cases had c.379C>T (p.Arg127Trp) missense mutation on exon 2 of CYP27A1 gene. They all had compound heterozygous mutation and two cases had new type of exon and intron compound mutation. This article enriched the types of CYP27A1 gene mutations in CTX patients. The primers of CYP27A1 gene should also cover more gene sequences including intron regions.
RESUMEN
Objective To investigate the causative mutations of CYP27A1 gene in a sporadic cerebrotendinous xanthomatosis patient. Methods Genomic DNA was extracted from peripheral blood of the patient and her parents. All exons and splice sites of CYP27A1 gene were amplified by polymerase chain reaction (PCR) followed by Sanger sequenc-ing. 105 healthy unrelated subjects were also sequenced for the novel mutation in CYP27A1. Results A novel splice site mutation c.446+1G>T, a novel missense mutation c.877A>T(p.Met293Leu) and a known missense mutation c.1016C>T (p.Thr339Met) of CYP27A1 gene were identified in the patient. The mother carriers the two novel mutations and the fa-ther the c.1016C>T(p.Thr339Met) mutation. The two novel mutations were absent in 105 control subjects, respectively. Conclusions Our study detected two novel mutations, c.446+1G>T and c.877A>T, as well as a known mutation c.1016C>T, of CYP27A1 in a sporadic cerebrotendinous xanthomatosis patient. Our data provide novel information for the mutational spectrum of the gene, which is applicable in the genetic testing and diagnosis. The data also provide in-sight into the pathogenesis of the disease.