Case Report: a novel CYP27A1 gene variant in a patient with cerebrotendinous xanthomatosis with unusual clinical findings

Abstract

Purpose/aim of the study

Cerebrotendinous xanthomatosis is a disease with important clinical and molecular heterogeneity. CYP27A1 gene was described as the cause of these defects, with more than 50 mutations involved in the disease. The objective of this study was to carry out a genetic study and a clinical description of a patient with unusual clinical manifestation of the disease.

Materials and methods

DNA sequencing was used for the evaluation of CYP27A1 exon sequences and their intron/exon boundaries. Copy number variants were calculated using a method based on depth of sequencing coverage. In addition, the potential effects of the missense variants were analyzed, and an in-silico protein modeling tool was used. Finally, a patient case description was performed in order to evaluate patient phenotype according to genetic results.

Results

Patient clinical features indicate the possible presence of a disease milder phenotype. When analyzing the CYP27A1 gene, patient presents a pathogenic variant (p.Arg474Trp) and a variant of unknown significance (p.Met130Ile) that causes a slight modification of the protein functional structure. This variant in homozygosis or double or compound heterozygosis together with other biallelic pathological mutations may be the cause of the clinical phenotype observed in the reported patient.

Conclusions

Clinical manifestations of cerebrotendinous xanthomatosis are heterogeneous, and sometimes wrongly suggest the presence of other diseases. Some patients seem to present an “incomplete” phenotype, which could be redefined as a variant of the disease with further studies. The evaluation of new mutations allows for earlier diagnosis and greater effectiveness in its treatment.

Keywords:

• Case report
• cerebrotendinous xanthomatosis
• clinical heterogeneity
• neurological involvement
• tendon xanthoma

Acknowledgments

Authors thank some professionals for their participation in conducting the exams: Aldo Ronquillo Soxo, José Manuel Vera Ruela, Lenin Jaime Reyes, Dennis Castañeda Cruz, Alejandro Apolo, Carlos Vincent Centeno, Lito Campos Carbo and Juan Carlos Burbano Machuca. UG Internal Medicine Chair. Students: Jorge Burga.

Author contributions

FATV was involved in the literature review, study design, clinical data collection, interpretation of observations and manuscript preparation. DCM was involved in the literature review, molecular analysis, and manuscript preparation. FATS was involved in the literature review and clinical data collection. MATS was involved in the literature review and clinical data collection.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.