Clinical and genetic characterization of Chanarin-Dorfman syndrome patients: first report of large deletions in the ABHD5 gene.

[lamellar ichthyosis]

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 . The clinical phenotype involves multiple organs and systems , including liver , eyes , ears , skeletal muscle and central nervous system (CNS ). Mutations in ABHD 5 /CGI 58 gene are associated with CDS .E ight CDS patients belonging to six different families from Mediterranean countries were enrolled for genetic study . Molecular analysis of the ABHD 5 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 ABHD 5 cDNAs .F ive different mutations were identified , four of which were novel , including two splice-site mutations (c .47 +1 G >A and c .960 +5 G >A ) and two large deletions (c .898 _*320 del and c .662 -1330 _773 +46 del ). 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 .These 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 .

Diseases
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Diseases presenting "early stop codon" symptom

lamellar ichthyosis

wiskott-aldrich syndrome

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