Biallelic variants in AGMO with diminished enzyme activity are associated with a neurodevelopmental disorder.
Hum Genet
; 138(11-12): 1259-1266, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31555905
Alkylglycerol monooxygenase (AGMO) is the only enzyme known to cleave the O-alkyl bonds of ether lipids (alkylglycerols) which are essential components of cell membranes. A homozygous frameshift variant [p.(Glu324LysfsTer12)] in AGMO has recently been reported in two male siblings with syndromic microcephaly. In this study, we identified rare nonsense, in frame deletion, and missense biallelic variants in AGMO in two unrelated individuals with neurodevelopmental disabilities. We assessed the activity of seven disease associated AGMO variants including the four variants identified in our two affected individuals expressed in human embryonic kidney (HEK293T) cells. We demonstrated significantly diminished enzyme activity for all disease-associated variants, supporting the mechanism as decreased AGMO activity. Future mechanistic studies are necessary to understand how decreased AGMO activity leads to the neurologic manifestations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos do Neurodesenvolvimento
/
Oxigenases de Função Mista
/
Mutação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos