Abstract

BackgroundChanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder characterized by nonbullous congenital ichthyosiform erythroderma (NCIE) and an intracellular accumulation of triacylglycerol (TG) droplets in most tissues. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system (CNS). Mutations in ABHD5/CGI58 gene are associated with CDS.MethodsEight CDS patients belonging to six different families from Mediterranean countries were enrolled for genetic study. Molecular analysis of the ABHD5 gene included the sequencing of the 7 coding exons and of the putative 5' regulatory regions, as well as reverse transcript-polymerase chain reaction analysis and sequencing of normal and aberrant ABHD5 cDNAs.ResultsFive different mutations were identified, four of which were novel, including two splice-site mutations (c.47+1G>A and c.960+5G>A) and two large deletions (c.898_*320del and c.662-1330_773+46del). All the reported mutations are predicted to be pathogenic because they lead to an early stop codon or a frameshift producing a premature termination of translation. While nonsense, missense, frameshift and splice-site mutations have been identified in CDS patients, large genomic deletions have not previously been described.ConclusionsThese results emphasize the need for an efficient approach for genomic deletion screening to ensure an accurate molecular diagnosis of CDS. Moreover, in spite of intensive molecular screening, no mutations were identified in one patient with a confirmed clinical diagnosis of CDS, appointing to genetic heterogeneity of the syndrome.

Highlights

  • Neutral-lipid storage diseases (NLSDs) are a clinically heterogeneous group of non-lysosomal inherited disorders characterized by the cytoplasmic accumulation of lipid droplets (LDs) in most tissues

  • Chanarin-Dorfman syndrome (CDS) is inherited as an autosomal recessive disorder and has been reported in approximately 55 cases, in families whose origins are in the Mediterranean area and the Middle-East [13]

  • Patients The two main clinical features of CDS (i.e. nonbullous congenital ichthyosiform erythroderma (NCIE) and hepatomegaly or liver steatosis) were present in all families investigated in this study, but with considerable variation in the extent and degree of organ involvement in individual patients (Table 1)

Read more

Summary

Introduction

Neutral-lipid storage diseases (NLSDs) are a clinically heterogeneous group of non-lysosomal inherited disorders characterized by the cytoplasmic accumulation of lipid droplets (LDs) in most tissues. When non-bullous congenital ichthyosiform erythroderma (NCIE), presenting as fine scaling on erythematous skin, is the dominant number of tissues other than adipose accumulate TGs in LDs even in the absence of an excess of circulating FAs. CDS is inherited as an autosomal recessive disorder and has been reported in approximately 55 cases, in families whose origins are in the Mediterranean area and the Middle-East [13]. Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder characterized by nonbullous congenital ichthyosiform erythroderma (NCIE) and an intracellular accumulation of triacylglycerol (TG) droplets in most tissues.

Methods
Results
Discussion
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.