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

Anide Johansen; Rasim O Rosti; Damir Musaev; Evan Sticca; Ricardo Harripaul; Maha Zaki; Ahmet Okay Çağlayan; Matloob Azam; Tipu Sultan; Tawfiq Froukh; André Reis; Bernt Popp; Iltaf Ahmed; Peter John; Muhammad Ayub; Tawfeg Ben-Omran; John B Vincent; Joseph G Gleeson; Rami Abou Jamra

doi:10.1016/j.ajhg.2016.07.019

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. Epub 2016 Sep 8.

Authors

Anide Johansen¹, Rasim O Rosti², Damir Musaev², Evan Sticca³, Ricardo Harripaul⁴, Maha Zaki⁵, Ahmet Okay Çağlayan⁶, Matloob Azam⁷, Tipu Sultan⁸, Tawfiq Froukh⁹, André Reis¹⁰, Bernt Popp¹⁰, Iltaf Ahmed¹¹, Peter John¹¹, Muhammad Ayub¹², Tawfeg Ben-Omran¹³, John B Vincent⁴, Joseph G Gleeson¹⁴, Rami Abou Jamra¹⁵

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.

MeSH terms

Acyltransferases / genetics*
Acyltransferases / metabolism
Arachidonic Acid / metabolism
Autistic Disorder / complications
Autistic Disorder / enzymology
Autistic Disorder / genetics*
Autistic Disorder / metabolism
Child
Child, Preschool
Consanguinity
Epilepsy / complications
Epilepsy / enzymology
Epilepsy / genetics*
Epilepsy / metabolism
Female
Homozygote
Humans
Infant
Intellectual Disability / complications
Intellectual Disability / enzymology
Intellectual Disability / genetics*
Intellectual Disability / metabolism
Lysophospholipids / metabolism
Male
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mutation*
Pedigree
Phosphatidylinositols / metabolism

Substances

Lysophospholipids
Membrane Proteins
Phosphatidylinositols
lysophosphatidylinositol
Arachidonic Acid
Acyltransferases
MBOAT7 protein, human
lysophosphatidylinositol acyltransferase

Abstract

MeSH terms

Substances

Grants and funding