1. Academic Validation
  2. Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features

Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features

  • Am J Hum Genet. 2016 Oct 6;99(4):912-916. doi: 10.1016/j.ajhg.2016.07.019.
Anide Johansen 1 Rasim O Rosti 2 Damir Musaev 2 Evan Sticca 3 Ricardo Harripaul 4 Maha Zaki 5 Ahmet Okay Çağlayan 6 Matloob Azam 7 Tipu Sultan 8 Tawfiq Froukh 9 André Reis 10 Bernt Popp 10 Iltaf Ahmed 11 Peter John 11 Muhammad Ayub 12 Tawfeg Ben-Omran 13 John B Vincent 4 Joseph G Gleeson 14 Rami Abou Jamra 15
Affiliations

Affiliations

  • 1 Laboratory for Pediatric Brain Disease, Department of Neurosciences, Rady Children's Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo 0316, Norway.
  • 2 Laboratory for Pediatric Brain Disease, Department of Neurosciences, Rady Children's Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • 3 Laboratory for Pediatric Brain Disease, Rockefeller University, New York, NY 10065, USA.
  • 4 Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON M5T 1R8, Canada.
  • 5 Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
  • 6 Department of Medical Genetics, School of Medicine, Istanbul Bilim University, Istanbul 34394, Turkey.
  • 7 Department of Pediatrics and Child Neurology, Wah Medical College, Wah Cantt, Pakistan.
  • 8 Department of Pediatric Neurology, Institute of Child Health, Children Hospital Lahore, Lahore 54000, Pakistan.
  • 9 Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan.
  • 10 Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • 11 Atta-ur-Rehman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
  • 12 Department of Psychiatry, Queen's University, Kingston, ON K7L 3N6, Canada.
  • 13 Clinical and Metabolic Genetics Department, Weill Cornell Medical College, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
  • 14 Laboratory for Pediatric Brain Disease, Department of Neurosciences, Rady Children's Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Laboratory for Pediatric Brain Disease, Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: jogleeson@mail.rockefeller.edu.
  • 15 Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Institute of Human Genetics, University Medical Center Leipzig, 04103 Leipzig, Germany.
Abstract

The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol Acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling Enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol. This study suggests a role for AA-containing phosphatidylinositols in the development of ID accompanied by epilepsy and autistic features.

Keywords

LPIAT1; MBOAT7; arachidonic acid; autism; epilepsy; inflammation; intellectual disability; lipid; phosphatidylinositol.

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