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Human Genetics

, Volume 138, Issue 11–12, pp 1259–1266 | Cite as

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

  • Volkan Okur
  • Katrin Watschinger
  • Dmitriy Niyazov
  • Julie McCarrier
  • Donald Basel
  • Martin Hermann
  • Ernst R. WernerEmail author
  • Wendy K. ChungEmail author
Original Investigation
  • 116 Downloads

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.

Notes

Acknowledgements

We thank the families for their generous contribution, and Petra Loitzl, Nina Madl, and Rita Holzknecht for expert technical assistance. This work was supported by Grants from Austrian Science Fund (fwf) projects to Katrin Watschinger (P30800) and Ernst R. Werner (P28769), and the SFARI and the JPB Foundation to Wendy K. Chung.

Author contributions

VO analyzed the data, drafted and critically reviewed the manuscript. KW analyzed the data, drafted and critically reviewed the manuscript. DN provided with the clinical data, critically reviewed the manuscript. JM provided with the clinical data, critically reviewed the manuscript. DB provided with the clinical data, critically reviewed the manuscript. MH analyzed the data and critically reviewed the manuscript. ERW conceived of the study, analyzed the data, drafted, and critically reviewed the manuscript. WKC conceived of the study, analyzed the data, drafted and critically reviewed the manuscript.

Compliance with ethical standards

Conflict of Interest

The authors declare no competing interests related to presented study.

Supplementary material

439_2019_2065_MOESM1_ESM.xlsx (22 kb)
Supplementary material 1 (XLSX 21 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Volkan Okur
    • 1
  • Katrin Watschinger
    • 2
  • Dmitriy Niyazov
    • 3
  • Julie McCarrier
    • 4
  • Donald Basel
    • 4
  • Martin Hermann
    • 5
  • Ernst R. Werner
    • 2
    Email author
  • Wendy K. Chung
    • 1
    • 6
    Email author
  1. 1.Department of PediatricsColumbia University Medical CenterNew YorkUSA
  2. 2.Institute of Biological Chemistry, Biocenter, Center for Chemistry and Biomedicine (CCB)Medical University of InnsbruckInnsbruckAustria
  3. 3.Department of PediatricsOchsner ClinicNew OrleansUSA
  4. 4.Department of PediatricsMedical College of WisconsinMilwaukeeUSA
  5. 5.Department of Anesthesiology and Critical Care MedicineMedical University of InnsbruckInnsbruckAustria
  6. 6.Department of MedicineColumbia University Medical CenterNew YorkUSA

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