Biallelic variants in AGMO with diminished enzyme activity are associated with a neurodevelopmental disorder. Hum Genet 2019 Dec;138(11-12):1259-1266
Date
09/27/2019Pubmed ID
31555905DOI
10.1007/s00439-019-02065-xScopus ID
2-s2.0-85074022538 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Okur V, Watschinger K, Niyazov D, McCarrier J, Basel D, Hermann M, Werner ER, Chung WKAuthor
Donald Basel MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesHEK293 Cells
Humans
Male
Mixed Function Oxygenases
Mutation
Neurodevelopmental Disorders
Prognosis
