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

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.

PMID: 27616480
PMCID: PMC5065650
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

Anide Johansen et al. Am J Hum Genet. 2016.

. 2016 Oct 6;99(4):912-916.

doi: 10.1016/j.ajhg.2016.07.019. Epub 2016 Sep 8.

Authors

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.

PMID: 27616480
PMCID: PMC5065650
DOI: 10.1016/j.ajhg.2016.07.019

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.

PubMed Disclaimer

Figures

**Figure 1**
Consanguineous Families with Variants in *MBOAT7*, Encoding LPIAT1 (A) Pedigrees of families 1 to 6 show consanguineous marriages (double bars) with a total of 16 affected children. Probands are indicated with “P.” (B) Brain MRI for one affected individual from each of families 1–3 and 6. White arrows show cortical atrophy, and red arrows show possible polymicrogyria.

**Figure 2**
Location of Variants and Domains in *MBOAT7*, Encoding LPIAT1 (A) Genetic structure of *MBOAT7*. Mutations are indicated by red arrows (exons and numbers as in GenBank: NM_024298.3). In-solution exome capture was performed with the SureSelect Human All Exome 50 Mb Kit (Agilent Technologies) with 125 bp paired-end read sequences generated on a HiSeq2000 or HiSeq2500 (Illumina). Scale bar represents 2 kb. (B) Structure of LPIAT1, which harbors five transmembrane domains and one catalytic acyltransferase domain. Variants are indicated with red lines. Amino acid numbers are provided above.

See this image and copyright information in PMC

References

1. Maulik P.K., Mascarenhas M.N., Mathers C.D., Dua T., Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Res. Dev. Disabil. 2011;32:419–436. - PubMed
1. Vissers L.E., Gilissen C., Veltman J.A. Genetic studies in intellectual disability and related disorders. Nat. Rev. Genet. 2016;17:9–18. - PubMed
1. American Psychiatric Association . American Psychiatric Publishing; 2013. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
1. Gilissen C., Hehir-Kwa J.Y., Thung D.T., van de Vorst M., van Bon B.W., Willemsen M.H., Kwint M., Janssen I.M., Hoischen A., Schenck A. Genome sequencing identifies major causes of severe intellectual disability. Nature. 2014;511:344–347. - PubMed
1. Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L., Massicotte C., Ambalavanan A., Spiegelman D., Diallo O. De novo mutations in moderate or severe intellectual disability. PLoS Genet. 2014;10:e1004772. - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

R01 NS098004/NS/NINDS NIH HHS/United States

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information
Molecular Biology Databases
- GlyGen glycoinformatics resource
- The Weizmann Institute of Science GeneCards and MalaCards databases
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous