A novel mutation of ABHD5 gene in a Chanarin Dorfman patient with unusual dermatological findings.

Abstract

BACKGROUND:

Chanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by the multisytemic accumulation of neutral lipids inside the cytoplasmic lipid droplets. This condition is caused by mutations in the abhydrolase domain containing 5 gene (ABHD5). In CDS the skin involvement is the prevalent and always observed clinical feature, consisting of a non-bullous congenital ichthyosiform erythroderma (NCIE). Moreover, a variable involvement of the liver and neuromuscular system can be also observed. In this report, we aimed to perform the clinical and genetic characterization of a patient affected by CDS with atypical dermatological findings, considering this rare inborn error of neutral lipid metabolism.

METHODS:

Genomic DNA samples obtained from patient and his parents were used to perform the sequencing of the ABHD5 exons and their intron/exon boundaries. Bioinformatic analyses were performed to investigate the possible effect of the identified mutation on protein structure.

RESULTS:

Here we present the case of a 29-year-old male patient with CDS, who, for long time, has been misdiagnosed as pityriasis rubra pilaris (PRP). He has a history of increasing hyperlipidemia; hepatomegaly associated with hepatosteatosis was also detected. ABHD5 molecular analysis revealed a novel missense mutation, the c.811G > A (p.G271R). Bioinformatic investigations showed that the variant has a deleterious effect on ABHD5 function, probably causing an incorrect folding of the mutant protein.

CONCLUSIONS:

These results highlihts the importance of genetic testing for ABHD5 in unresolved cases of patients presenting unusual skin lesions, that resemble PRP, associated with a history of hyperlipidemia and nonalcoholic fatty liver.

• Authors: Ali Haydar Eskiocak, Sara Missaglia, Laura Moro, Murat Durdu, Daniela Tavian
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 18 Issue 1 Pg. 232 (Dec 28 2019) ISSN: 1476-511X [Electronic] England
• PMID: 31883530 (Publication Type: Case Reports, Journal Article)

Chemical References

• Lipids
• 1-Acylglycerol-3-Phosphate O-Acyltransferase
• ABHD5 protein, human

Topics

• 1-Acylglycerol-3-Phosphate O-Acyltransferase (genetics)
• Adult
• Diagnostic Errors
• Genetic Predisposition to Disease
• Humans
• Ichthyosiform Erythroderma, Congenital (diagnosis, genetics, pathology)
• Ichthyosis, Lamellar (diagnosis, genetics, pathology)
• Lipid Droplets (metabolism)
• Lipid Metabolism, Inborn Errors (diagnosis, genetics, pathology)
• Lipids (genetics)
• Male
• Muscular Diseases (diagnosis, genetics, pathology)
• Mutation, Missense
• Pityriasis Rubra Pilaris (diagnosis, genetics, pathology)
• Protein Folding