Biallelic variants in AGMO with diminished enzyme activity are associated with a neurodevelopmental disorder Article

Full Text via DOI: 10.1007/s00439-019-02065-x PMID: 31555905 Web of Science: 000498476100006
International Collaboration

Cited authors

  • Okur, Volkan; Watschinger, Katrin; Niyazov, Dmitriy; McCarrier, Julie; Basel, Donald; Hermann, Martin; Werner, Ernst R.; Chung, Wendy K.

Abstract

  • 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.

Publication date

  • 2019

Published in

Category

International Standard Serial Number (ISSN)

  • 0340-6717

Start page

  • 1259

End page

  • 1266

Volume

  • 138

Issue

  • 11-12