TY - JOUR
T1 - Clinical and genetic characterization of Chanarin-Dorfman Syndrome patients: first report of large deletions in the ABHD5
AU - Redaelli, Chiara
AU - Coleman, Rosalind A.
AU - Moro, Laura
AU - Dacou Voutetakis, Catherine
AU - Elsayed, Sm
AU - Prati, Daniele
AU - Colli, Alessandro
AU - Mela, Donatella
AU - Colombo, Roberto
AU - Tavian, Daniela
PY - 2010
Y1 - 2010
N2 - Abstract
Background
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 ABHD5/CGI58 gene are associated with CDS.
Methods
Eight 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.
Results
Five 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.
Conclusions
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.
AB - Abstract
Background
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 ABHD5/CGI58 gene are associated with CDS.
Methods
Eight 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.
Results
Five 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.
Conclusions
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.
KW - ABHD5 gene
KW - ATGL gene
KW - Chanarin-Dorfman
KW - Neutral lipid storage disorders
KW - large deletions
KW - lipid droplets
KW - ABHD5 gene
KW - ATGL gene
KW - Chanarin-Dorfman
KW - Neutral lipid storage disorders
KW - large deletions
KW - lipid droplets
UR - http://hdl.handle.net/10807/20803
U2 - 10.1186/1750-1172-5-33
DO - 10.1186/1750-1172-5-33
M3 - Article
SN - 1750-1172
VL - 5
SP - N/A-N/A
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
ER -