A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency.
Am J Med Genet A
; 191(4): 1089-1093, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36579410
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa
/
Proteínas Hierro-Azufre
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Newborn
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos