Clinical and Genetic Characteristics of Splicing Variant in CYP27A1 in an Iranian Family with Cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare inborn lipid-storage disease leading to a progressive multisystem disease. CTX with autosomal recessive inheritance is caused by a defect in the CYP27A1 gene. Hallmark clinical manifestations of CTX include bilateral cataracts, chronic diarrhea, tendon xanthomas, and neurologic dysfunction. CTX 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. In this study, we report for the first time a non-relative Iranian family from the same origin with three CTX siblings with c.1184+1G>A mutation in the CYP27A1 gene. 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 analysed. There is no correlation between genotype and phenotype, which is another characteristic of this disease. The CYP27A1 gene was also studied for the number of pathogenic variants and their location. Among the pathogenic variants, splice site mutation had the highest prevalence and the mutations were mostly in exon 4. Increasing awareness is a key step in improving outcomes for patients with CTX, who are often diagnosed in adulthood after a significant delay (~20 years) between symptom onset and diagnosis.