A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency.
ETFA
MADD
electron transfer flavoprotein
glutaric acidemia II
glutaric aciduria II
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
08
12
2022
received:
21
10
2022
accepted:
10
12
2022
pubmed:
30
12
2022
medline:
15
3
2023
entrez:
29
12
2022
Statut:
ppublish
Résumé
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism. We describe a patient identified through newborn screening in which the diagnosis of MADD was confirmed based on metabolic profiling, but clinical molecular sequencing of ETFA, ETFB, and ETFDH was normal. In order to identify the genetic etiology of MADD, we performed whole genome sequencing and identified a novel homozygous promoter variant in ETFA (c.-85G > A). Subsequent studies showed decreased ETFA protein expression in lymphoblasts. A promoter luciferase assay confirmed decreased activity of the mutant promoter. In both assays, the variant displayed considerable residual activity, therefore we speculate that our patient may have a late onset form of MADD (Type III). Our findings may be helpful in establishing a molecular diagnosis in other MADD patients with a characteristic biochemical profile but apparently normal molecular studies.
Identifiants
pubmed: 36579410
doi: 10.1002/ajmg.a.63104
doi:
Substances chimiques
Electron-Transferring Flavoproteins
0
Amino Acids
0
Iron-Sulfur Proteins
0
ETFA protein, human
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
1089-1093Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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