Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation.
BBA Clin
; 5: 114-9, 2016 Jun.
Article
in En
| MEDLINE
| ID: mdl-27051597
ABSTRACT
Short-chain acyl-coA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation caused by ACADS gene alterations. SCADD is a heterogeneous condition, sometimes considered to be solely a biochemical condition given that it has been associated with variable clinical phenotypes ranging from no symptoms or signs to metabolic decompensation occurring early in life. A reason for this variability is due to SCAD alterations, such as the common p.Gly209Ser, that confer a disease susceptibility state but require a complex multifactorial/polygenic condition to manifest clinically. Our study focuses on 12 SCADD patients carrying 11 new ACADS variants, with the purpose of defining genotype-phenotype correlations based on clinical data, metabolite evaluation, molecular analyses, and in silico functional analyses. Interestingly, we identified a synonymous variant, c.765G > T (p.Gly255Gly) that influences ACADS mRNA splicing accuracy. mRNA characterisation demonstrated that this variant leads to an aberrant splicing product, harbouring a premature stop codon. Molecular analysis and in silico tools are able to characterise ACADS variants, identifying the severe mutations and consequently indicating which patients could benefit from a long term follow- up. We also emphasise that synonymous mutations can be relevant features and potentially associated with SCADD.
ACADS; ACADS, Acyl CoA-deydrogenase, short chain; C4-C, butyrylcarnitine; EMA, ethylmalonic acid; LCMS/MS, Tandem mass spectrometry; NBS, Newborn screening; SCAD; SCAD, Short-chain acyl-CoA dehydrogenase; SCADD, Short-chain acyl-CoA dehydrogenase deficiency; Short-chain acyl-CoA dehydrogenase; Synonymous mutation
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
BBA Clin
Year:
2016
Document type:
Article
Affiliation country:
Italia