Clinical And Genetic Research Of Cerebrotendinous Xanthomatosis Caused By CYP27A1 Gene Mutation

Objective:The clinical phenotypes and genotypes of 4 patients with Cerebrotendinous Xanthomatosis(CTX)were analyzed,and the clinical significance of CYP27A1 gene mutation was studied.Methods:The clinical data of 4 patients with cerebrotendinous xanthomatosis were collected and sorted out.The peripheral blood DNA of CTX patients was extracted by phenol-chloroform method,whole exome sequencing was performed on the samples.The test results were verified and analyzed by polymerase chain reaction and Sanger sequencing.Through DNA extraction from peripheral blood,the siginificance of CYP27A1 gene mutation was analyzed by using haplotype analysis.The clinical significance of CYP27A1 gene mutation was studied by retrospectively analyzing the previously reported cerebrotendinous xanthomatosis.Results:Through clinical phenotypic review and genetic analysis,we have diagnosed a total of 4 patients with cerebrotendinous xanthomatosis,including 2 male and 2 female patients.The general age of onset of CTX is 7 to 14 years,the average age is 9.5 years,and the general course of disease is 17 to 25 years,and the average course of disease is 22 years.The CTX patients in our study were mainly characterized by weakness of the lower limb,walking instability,and speech disorders as the first clinical manifestations.Physical examination showed increased bilateral tendon reflexes,positive Babinski sign,and positive finger-to-nasal test.Two CTX patients had high arched feet deformity.According to the whole exome sequencing and Sanger sequencing verification,the four probands are all compound heterozygotes of two CYP27A1 gene variants,including a mutation at the splice site of c.1263+1G>A(intron 7).Two new possible pathogenic mutations(c.255+1G>T and c.1561dupA)and three previously reported pathogenic mutations,including c.379C>T,c.1263+1G>A and c.1537C>T.SNP showed that CYP27A1 gene has partial haplotype identity at c.1263+1 G>A mutation site.Conclusion:CTX is a rare autosomal recessive inherited lipid metabolism disease.This study identified 4 probands as CTX patients.The genetic tests are all compound heterozygotes of two variants of CYP27A1,including c.1263+1G>A(intron 7)splice site mutations,c.255+1G>T and c.1561dupA two new possible pathogenic mutations,and c.379C>T,c.1263+1G>A and c.1537C>T three pathogenic mutations.c.1263+1G>A gene mutation is very common in the number of reported cases in my country(7/25,28%),so it may be a potential hot spot for CYP27A1 gene mutation in Chinese CTX patients.Through SNP haplotype analysis,it is concluded that the mutation site of c.1263+1G>A gene has clinical pathogenic significance.The diagnosis of CTX is usually determined based on clinical manifestations,neuroimaging,blood biochemical testing,and genetic analysis.Early diagnosis of CTX is the key to start and chenodeoxycholic acid(CDCA)treatment as early as possible,which can effectively reverse and prevent the progression of related clinical symptoms.Figure3 table5 reference8 8...