Chanarin Dorfman syndrome: a case report with novel nonsense mutation

Gupta, Neerja; Gothwal, Sunil; Satpathy, Amit Kumar; Missaglia, Sara; Tavian, Daniela; Das, Prasenjit; Dipsal, Timila; Kabra, Madhulika

doi:10.1016/j.gene.2015.09.004

Cited by 11 publications

(11 citation statements)

References 13 publications

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“…Currently, there is no specific treatment for CDS. However, a diet low in fatty acids with medium chain triglycerides (MCT) supplementation was reported to decrease hepatomegaly and normalize hepatic enzymes, especially when early initiated in combination with vitamin E and ursodeoxycholic acid [4,7,[13][14][15]. Although our patient is now 29 years old, after molecular testing, we have recommended a fat-restricted diet+MCT because he presented hepatomegaly, hepatosteatosis and elevation in liver function tests.…”

Section: Discussionmentioning

confidence: 90%

“…The clinical diagnosis is based on detection of Jordans' bodies (JBs), characteristic cytoplasmatic vacuoles in the granulocytes of patients [2]. To date, 150 cases have been described worldwide [3,4]. Many of them have been reported from the Mediterranean and Middle-East region, especially Turkey, where consanguineous marriages are still common [5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…In CDS, muscle abnormalities have been detected in 40% of subjects. Myopathy typically begins in the thirties, but it has also been described in very young children [ 2 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents

et al. 2018

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BackgroundChanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by ichthyosiform non-bullous erythroderma and variable involvement of the liver and the neuromuscular system. In CDS patients, the accumulation of neutral lipids inside cytoplasmic lipid droplets has been demonstrated in different tissues. To date, ninety families with this disease have been described worldwide; most of them are from Mediterranean countries.Case presentationIn this report, we describe a consanguineous Turkish family with typical features of CDS. The parents are first cousins and are both diseased. At the age of eight, their child presented CDS with non-bullous congenital ichthyosiform erythroderma, hepatosteatosis, hepatomegaly and ectropion. Electromyographic examination is compatible with myopathy. A five-year-old cousin of the child is also affected by CDS. She was born to non-affected consanguineous parents. Mutation analysis of the ABHD5 gene revealed the previously reported mutation, N209X, which is the most frequent in Turkish patients. Lipid vacuoles, also known as Jordan’s anomaly, are detectable in their leucocytes.ConclusionsTo the best of our knowledge, this is the first report of a CDS family in which both parents and their child are affected by CDS. To date, the child does not present a more severe clinical phenotype compared with those of his relatives or other CDS patients of the same age. These findings suggest that high levels of triacylglycerol accumulation, that may be supposed to be present in high amount inside the ooplasm, did not affect embryo development and foetal growth.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0610-0) contains supplementary material, which is available to authorized users.

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“…While ichthyosis is always present, others clinical features may vary. Liver involvement is observed in greater than 80% of patients, ranging from hepatomegaly or liver steatosis to cirrhosis [31,61,62,63]. Sensorineural hearing loss is present in almost 30% of NLSDI patients.…”

Section: Neutral Lipid Storage Disordersmentioning

confidence: 99%

“…In NLSDI patients, liver biopsies reveal intra-hepatocyte lipid vacuoles that are much larger (several microns in diameter) than those found in control liver (0.5–2 µm) (Figure 5E). These LDs are both microvesicular (accumulation of small LDs in hepatocytes with preserved cellular architecture) and macrovesicular (larger droplets that displace the nucleus) [60,61,62,63]. Sometimes, both fibrosis and cirrhosis can be detected [38].…”

Section: Lds In Nlsd Patient Tissuesmentioning

confidence: 99%

Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function

Missaglia

Coleman

Mordente

et al. 2019

Cells

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Neutral lipid storage disease with myopathy (NLSDM) and with ichthyosis (NLSDI) are rare autosomal recessive disorders caused by mutations in the PNPLA2 and in the ABHD5/CGI58 genes, respectively. These genes encode the adipose triglyceride lipase (ATGL) and α-β hydrolase domain 5 (ABHD5) proteins, which play key roles in the function of lipid droplets (LDs). LDs, the main cellular storage sites of triacylglycerols and sterol esters, are highly dynamic organelles. Indeed, LDs are critical for both lipid metabolism and energy homeostasis. Partial or total PNPLA2 or ABHD5/CGI58 knockdown is characteristic of the cells of NLSD patients; thus, these cells are natural models with which one can unravel LD function. In this review we firstly summarize genetic and clinical data collected from NLSD patients, focusing particularly on muscle, skin, heart, and liver damage due to impaired LD function. Then, we discuss how NLSD cells were used to investigate and expand the current structural and functional knowledge of LDs.

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Chanarin Dorfman syndrome: a case report with novel nonsense mutation

Cited by 11 publications

References 13 publications

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

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

Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents

Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function

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