A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family

A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family Publisher Pubmed

Binaafar S¹ ; Razmara E² ; Mahdieh N¹ ; Sahebjame H³ ; Tavasoli AR⁴ ; Garshasbi M⁵

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1. Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2. Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia
3. Department of Biology, Faculty of Basic Science, Gonbad Kavous University, Gonbad Kavous, Golestan, Iran
4. Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
5. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: European Journal of Medical Genetics Published:2020

Abstract

Intellectual disability (ID) affects 1–3% of the general population worldwide. Genetic factors play an undeniable role in the etiology of Non-Syndromic Intellectual disability (NS-ID). Nowadays, whole-exome sequencing (WES) technique is used frequently to identify the causative genes in such heterogeneous diseases. Herein, we subjected four patients with initial diagnostics of NS-ID in a consanguineous Iranian family. To find the possible genetic cause(s), Trio-WES was performed on the proband and his both healthy parents. Sanger sequencing was performed to confirm the identified variant by WES and also investigate whether it co-segregates with the patients’ phenotype in the family. Using several online in-silico predictors, the probable impacts of the variant on structure and function of GPT2 protein were predicted. A novel variant, c.266A>G; p.(Glu89Gly), in exon 3 of GPT2 (NM_133443.3) was identified using Trio-WES. The candidate variant was also verified by Sanger sequencing. All affected members showed the common clinical features suffering from a non-progressive mild-to-severe ID. Also, different clinical observations compared to previously reported cases such as no facial features, no obvious structural malformations, ability to speak but with difficulty, and lack of any morphological defects were noted for the first time in this family. The c.266A>G; p.(Glu89Gly) variant reported here is the sixth variant identified up to now in the GPT2 gene, to be associated with NS-ID. Our data support the potential malfunction of the substituted GPT2 protein resulted from the novel variant, however, we strongly suggest confirming this finding more by doing functional analysis. © 2020 Elsevier Masson SAS

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Ali Reza Tavasoli (6)

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Style	Citing Format
MLA	Binaafar S, et al.. "A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family." European Journal of Medical Genetics, vol. 63, no. 5, 2020, pp. -.
APA	Binaafar S, Razmara E, Mahdieh N, Sahebjame H, Tavasoli AR, Garshasbi M (2020). A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family. European Journal of Medical Genetics, 63(5), -.
Chicago	Binaafar S, Razmara E, Mahdieh N, Sahebjame H, Tavasoli AR, Garshasbi M. "A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family." European Journal of Medical Genetics 63, no. 5 (2020): -.
Harvard	Binaafar S et al. (2020) 'A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family', European Journal of Medical Genetics, 63(5), pp. -.
Vancouver	Binaafar S, Razmara E, Mahdieh N, Sahebjame H, Tavasoli AR, Garshasbi M. A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family. European Journal of Medical Genetics. 2020;63(5):-.
BibTex	@article{ author = {Binaafar S and Razmara E and Mahdieh N and Sahebjame H and Tavasoli AR and Garshasbi M}, title = {A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family}, journal = {European Journal of Medical Genetics}, volume = {63}, number = {5}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Binaafar S AU - Razmara E AU - Mahdieh N AU - Sahebjame H AU - Tavasoli AR AU - Garshasbi M TI - A Novel Missense Variant in Gpt2 Causes Non-Syndromic Autosomal Recessive Intellectual Disability in a Consanguineous Iranian Family JO - European Journal of Medical Genetics VL - 63 IS - 5 SP - EP - PY - 2020 ER -

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