A recurrent de novo ATP5F1A substitution associated with neonatal complex V deficiency.
Eur J Hum Genet
; 29(11): 1719-1724, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34483339
ABSTRACT
Mitochondrial disorders are a heterogeneous group of rare, degenerative multisystem disorders affecting the cell's core bioenergetic and signalling functions. Spontaneous improvement is rare. We describe a novel neonatal-onset mitochondriopathy in three infants with failure to thrive, hyperlactatemia, hyperammonemia, and apparent clinical resolution before 18 months. Exome sequencing showed all three probands to be identically heterozygous for a recurrent de novo substitution, c.620G>A [p.(Arg207His)] in ATP5F1A, encoding the α-subunit of complex V. Patient-derived fibroblasts exhibited multiple deficits in complex V function and expression in vitro. Structural modelling predicts the observed substitution to create an abnormal region of negative charge on ATP5F1A's ß-subunit-interacting surface, adjacent to the nearby ß subunit's active site. This disorder, which presents with life-threatening neonatal manifestations, appears to follow a remitting course; the long-term prognosis remains unknown.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Mitocondriais
/
ATPases Mitocondriais Próton-Translocadoras
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article