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

• Published in: Lipids in health and disease 2019-12, Vol.18 (1), p.232-232, Article 232
• Main Authors: Eskiocak, Ali Haydar, Missaglia, Sara, Moro, Laura, Durdu, Murat, Tavian, Daniela
• Format: Article
• Language: English
• Subjects: Analysis; Binding sites; Bone marrow; Chanarin-Dorfman syndrome; Disease; DNA; EDTA; Exons; Fatty liver; Genes; Genetic aspects; Genetic disorders; Genetic screening; Genetic testing; Hereditary diseases; Hyperlipidemia; Ichthyosis; Kinases; Lipid disorder; Lipid metabolism; Lipids; Liver; Liver diseases; Liver involvement; Medical research; Missense mutation; Musculoskeletal system; Mutants; Mutation; Nervous system; Neuromuscular system; Novels; Physiological aspects; Pityriasis; Pityriasis rubra pilaris; Protein folding; Protein structure; Proteins; Short Report; Skin; Skin diseases; Skin lesions
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-019-1181-6

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. 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. 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. 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.