Cerebrotendinous xanthomatosis (CTX) is a rare congenital lipid-storage disorder, leading to a progressive multisystem disease. CTX with autosomal recessive inheritance is caused by a defect in the CYP27A1 gene. Chronic diarrhea, tendon xanthomas, neurologic impairment, and bilateral cataracts arecommon symptoms of the disease.
Three affected siblings with an initial diagnosis of non-syndromic intellectual disability (NSID)was recruited for further molecular investigation. To identify the possible genetic cause(s), whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was applied to confirm the final variant. The clinical and molecular genetic features of the three siblings from the new CTX family and other patients with the same mutations as previously reported were analyzed. The CYP27A1 gene was also studied for the number of pathogenic variants and their location.
We found a homozygous splicing mutation, NM_000784: exon6: c.1184+1G>A in CYP27A1gene, and then was confirmed with Sanger sequencing. Among the pathogenic variants found intheCYP27A1 gene, splice site mutation had the highest prevalence, and the mutations were mostly in exon 4.
The mutation c.1184+1G>A is reported for the first time in Iran. There is nocorrelation between genotype and phenotype, which is another characteristic of this disease. TX is a rare disorder, which is supposed to be under-diagnosed, as presenting signs and symptoms maybe nonspecific with significant overlap with other more common conditions. Increasingawareness can lead to progress in the process of diagnosis and improvement of patients who are often recognized in adulthood.