Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability

Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability Publisher Pubmed

Heidari E¹ ; Caddeo A² ; Zarabadi K¹ ; Masoudi M³ ; Tavasoli AR³ ; Romeo S^{2, 4, 5} ; Garshasbi M¹

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1. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Sweden
3. Division of Pediatric Neurology, Children's Medical Center, Tehran University of Medical Sciences, Myelin Disorders Clinic, Tehran, Iran
4. Department of Cardiology, Sahlgrenska University Hospital, Sweden
5. Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Italy

Source: Genomics Published:2020

Abstract

The membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene codes for an enzyme involved in regulating arachidonic acid incorporation in lysophosphatidylinositol. Patients with homozygous nonsense mutations in MBOAT7 have intellectual disability (ID) accompanied with seizure and autism. Accumulating evidences obtained from human genetic studies have shown that MBOAT7 is also involved in fatty liver disease. Here we identified two novel homozygous variants in MBOAT7, NM_024298.5: c.1062C>A; p.(Tyr354*) and c.1135del; p.(Leu379Trpfs*9), in two unrelated Iranian families by means of whole exome sequencing. Sanger sequencing was performed to confirm the identified variants and also to investigate whether they co-segregate with the patients' phenotypes. To understand the functional consequences of these changes, we overexpressed recombinant wild type MBOAT7 and mutants in vitro and showed these mutations resulted in abolished protein synthesis and expression, indicating a complete loss of function. Albeit, we did not trace any liver diseases in our patients, but presence of globus pallidus signal changes in Magnetic Resonance Images might be indicative of metabolic changes as a result of loss of MBOAT7 expression in hepatic cells. These signal changes could also help as an important marker of MBOAT7 deficiency while analyzing the genomic data of patients with similar phenotypes. © 2020 Elsevier Inc.

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Style	Citing Format
MLA	Heidari E, et al.. "Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability." Genomics, vol. 112, no. 6, 2020, pp. 4072-4077.
APA	Heidari E, Caddeo A, Zarabadi K, Masoudi M, Tavasoli AR, Romeo S, Garshasbi M (2020). Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability. Genomics, 112(6), 4072-4077.
Chicago	Heidari E, Caddeo A, Zarabadi K, Masoudi M, Tavasoli AR, Romeo S, Garshasbi M. "Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability." Genomics 112, no. 6 (2020): 4072-4077.
Harvard	Heidari E et al. (2020) 'Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability', Genomics, 112(6), pp. 4072-4077.
Vancouver	Heidari E, Caddeo A, Zarabadi K, Masoudi M, Tavasoli AR, Romeo S, et al.. Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability. Genomics. 2020;112(6):4072-4077.
BibTex	@article{ author = {Heidari E and Caddeo A and Zarabadi K and Masoudi M and Tavasoli AR and Romeo S and Garshasbi M}, title = {Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability}, journal = {Genomics}, volume = {112}, number = {6}, pages = {4072-4077}, year = {2020} }
RIS	TY - JOUR AU - Heidari E AU - Caddeo A AU - Zarabadi K AU - Masoudi M AU - Tavasoli AR AU - Romeo S AU - Garshasbi M TI - Identification of Novel Loss of Function Variants in Mboat7 Resulting in Intellectual Disability JO - Genomics VL - 112 IS - 6 SP - 4072 EP - 4077 PY - 2020 ER -

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