Clinical and genetic characterization of chanarin-dorfman syndrome patients: first report of large deletions in the ABHD5 gene

Redaelli, Chiara; Coleman, Rosalind A.; Moro, Laura; Dacou-Voutetakis, Catherine; Elsayed, Solaf M.; Prati, Daniele; Colli, Agostino; Mela, Donatella; Colombo, Roberto; Tavian, Daniela

doi:10.1186/1750-1172-5-33

Cited by 47 publications

(47 citation statements)

References 31 publications

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“…In one, previously described, case (pt.XV.1) no mutations were detected in either the PNPLA2 or CGI58 genes [6], but both ichthyosis and Jordans’ anomaly were present.…”

Section: Resultsmentioning

confidence: 99%

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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BackgroundA small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases.ResultsDuring the clinical follow-up (range: 2–44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias.ConclusionThe genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases.

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“…In one, previously described, case (pt.XV.1) no mutations were detected in either the PNPLA2 or CGI58 genes [6], but both ichthyosis and Jordans’ anomaly were present.…”

Section: Resultsmentioning

confidence: 99%

Neutral Lipid Storage Diseases: clinical/genetic features and natural history in a large cohort of Italian patients

Pennisi

Arca

Bertini

et al. 2017

Orphanet J Rare Dis

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“…Currently, more than two dozen different mutations in the human CGI-58 gene are known including missense mutations, nonsense mutations, splice site mutations at exon-intron boundaries and insertion/deletion mutations 29–42. Importantly, all known NLSD patients, who are affected by mutations in the CGI-58 gene, suffer from ichthyosis.…”

Section: Mutations In the Gene Encoding “Comparative Gene Identificatmentioning

confidence: 99%

Fat in the skin

Radner¹,

Grond

Haemmerle³

et al. 2011

Dermato-Endocrinology

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Keratinocyte differentiation is essential for skin development and the formation of the skin permeability barrier. This process involves an orchestrated remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by β-glucocerebrosidase, sphingomyelinase, phospholipases and sterol sulfatase generates ceramides, non-esterified fatty acids and cholesterol for the lipid-containing extracellular matrix, the lamellar membranes in the stratum corneum. The importance of triacylglycerol (TAG) hydrolysis for the formation of a functional permeability barrier was only recently appreciated. Mice with defects in TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2-knock-out) or TAG catabolism (comparative gene identification-58, -CGI-58-knock-out) develop severe permeability barrier defects and die soon after birth because of desiccation. In humans, mutations in the CGI-58 gene also cause (non-lethal) neutral lipid storage disease with ichthyosis. As a result of defective TAG synthesis or catabolism, humans and mice lack ω-(O)-acylceramides, which are essential lipid precursors for the formation of the corneocyte lipid envelope. This structure plays an important role in linking the lipid-enriched lamellar membranes to highly cross-linked corneocyte proteins. This review focuses on the current knowledge of biochemical mechanisms that are essential for epidermal neutral lipid metabolism and the formation of a functional skin permeability barrier.

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“…In 2007, Fischer et al identified several mutations in PNPLA2 , proving that ATGL deficiency causes NLSD with myopathy, but without the ichthyiosis that is a distinct marker of CGI58 deficiency. Based on this, Fischer and colleagues suggested classifying ATGL deficiency as “NLSD with myopathy” (NLSD‐M), and CGI‐58 deficiency as “NLSD with ichthyosis” (NLSD‐I), a disorder previously known as Chanarin–Dorfman disease …”

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confidence: 99%