en Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله کامل Full Length/Original Article <strong>Background:</strong> 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 <em>CYP27A1</em> gene. Chronic diarrhea, tendon xanthomas, neurologic impairment, and bilateral cataracts are common symptoms of the disease. <strong>Methods: </strong>Three affected siblings with an initial diagnosis of non-syndromic intellectual disability were recruited for further molecular investigations. To identify the possible genetic cause(s), whole exome sequencing 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 <em>CYP27A1</em> gene was also studied for the number of pathogenic variants and their location. <strong>Results: </strong>We found a homozygous splicing mutation, NM_000784: exon6: c.1184+1G>A, in <em>CYP27A1 </em>gene, which was confirmed by Sanger sequencing. Among the detected pathogenic variants, the splice site mutation had the highest prevalence, and the mutations were mostly found in exon 4. <strong>Conclusion:</strong> This study is the first to report the c.1184+1G>A mutation in Iran. Our findings highlight the other feature of the disease, which is the lack of relationship between phenotype and genotype. Due to nonspecific symptoms and delay in diagnosis, CYP27A1&nbsp;genetic analysis should be the definitive method for CTX diagnosis. Cerebrotendinous xanthomatosis, CYP27A1, Intellectual disability, Iran, Whole exome sequencing 132 139 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-4099-1&slc_lang=en&sid=1 Zahra Rashvand z.rashvand125@gmail.com 0000-0001-9751-5286 No Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran Kimia Kahrizi kahrizi@yahoo.com 0000-0002-6587-7706 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Hossein Najmabadi hnajm12@yahoo.com 0000-0002-6084-7778 No Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Reza Najafipour rnajafipour@gmail.com 0000-0001-6042-8314 No Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran Mir Davood Omrani davood_omrani@sbmu.ac.ir 0000-0002-0673-9717 Yes Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran