Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features.
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.
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.
Anide
A
Johansen
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.
Rasim O
RO
Rosti
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.
Damir
D
Musaev
Laboratory for Pediatric Brain Disease, Rockefeller University, New York, NY 10065, USA.
Evan
E
Sticca
Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON M5T 1R8, Canada.
Ricardo
R
Harripaul
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Maha
M
Zaki
Department of Medical Genetics, School of Medicine, Istanbul Bilim University, Istanbul 34394, Turkey.
Ahmet Okay
AO
Çağlayan
Department of Pediatrics and Child Neurology, Wah Medical College, Wah Cantt, Pakistan.
Matloob
M
Azam
Department of Pediatric Neurology, Institute of Child Health, Children Hospital Lahore, Lahore 54000, Pakistan.
Tipu
T
Sultan
Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan.
Tawfiq
T
Froukh
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
André
A
Reis
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Bernt
B
Popp
Atta-ur-Rehman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Iltaf
I
Ahmed
Atta-ur-Rehman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Peter
P
John
Department of Psychiatry, Queen's University, Kingston, ON K7L 3N6, Canada.
Muhammad
M
Ayub
Clinical and Metabolic Genetics Department, Weill Cornell Medical College, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
Tawfeg
T
Ben-Omran
Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON M5T 1R8, Canada.
John B
JB
Vincent
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.
Joseph G
JG
Gleeson
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Institute of Human Genetics, University Medical Center Leipzig, 04103 Leipzig, Germany.
Rami
R
Abou Jamra
D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001321:Autistic Disorder / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004827:Epilepsy / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D010716:Phosphatidylinositols / Q000378:metabolism
D008246:Lysophospholipids; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C025449:lysophosphatidylinositol; D016718:Arachidonic Acid; D000217:Acyltransferases; C000616532:MBOAT7 protein, human; C021522:lysophosphatidylinositol acyltransferase
LPIAT1; MBOAT7; arachidonic acid; autism; epilepsy; inflammation; intellectual disability; lipid; phosphatidylinositol