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

Authors
  • Rashvand, Zahra1
  • Kahrizi, Kimia1
  • Najmabadi, Hossein2
  • Najafipour, Reza3
  • Omrani, Mir Davood1
  • 1 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
  • 2 GeneticsResearchCenter, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran;
  • 3 CellularandMolecularResearchCentre, Qazvin University of Medical Sciences, Qazvin, Iran
Type
Published Article
Journal
Iranian Biomedical Journal
Publisher
Pasteur Institute of Iran
Publication Date
Jan 19, 2021
Volume
25
Issue
2
Pages
132–139
Identifiers
DOI: 10.29252/ibj.25.2.132
PMID: 33400472
PMCID: PMC7921520
Source
PubMed Central
Keywords
Disciplines
  • Case Report
License
Green

Abstract

Background: 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 are common symptoms of the disease. Methods: 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), 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. Results: We found a homozygous splicing mutation, NM_000784: exon6: c.1184+1G>A, in CYP27A1 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. Conclusion: 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 genetic analysis should be the definitive method for CTX diagnosis.

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