A Homozygous Mutation in GPT2 Associated with Nonsyndromic Intellectual Disability in a Consanguineous Family from Costa Rica

Research Report
Part of the JIMD Reports book series (JIMD, volume 36)


Intellectual disability is a highly heterogeneous disease that affects the central nervous system and impairs patients’ ability to function independently. Despite multiples genes involved in the etiology of disease, most of the genetic background is yet to be discovered. We used runs of homozygosity and exome sequencing to study a large Costa Rican family with four individuals affected with severe intellectual disability and found a novel homozygous missense mutation, p. 96G>R, c. 286G>A, in all affected individuals. This gene encodes for a pyridoxal enzyme involved in the production of the neurotransmitter glutamate and is highly expressed in the white matter of brain and cerebellum. Protein modeling of GPT2 predicted that the mutation is located in a loop where the substrate binds to the active site of the enzyme, therefore, suggesting that the catalytic activity is impaired. With our report of a second mutation we fortify the importance of GPT2 as a novel cause of autosomal recessive nonsyndromic intellectual disability and support the premise that GPT2 is highly important for the neurodevelopment of the central nervous system.

Synopsis: The mutation p. 96G>R c. 286G>A in GPT2, located in a loop where the substrate binds to the active site of the enzyme, fortifies the importance of GPT2 in the pathogenesis of nonsyndromic intellectual disability.


Developmental delay GPT2 Intellectual disability Missense mutation Runs of homozygosity Vineland Social Maturity Scale 



We thank the patients and their family for the kind cooperation.


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Section of Genetics and Biotechnology, School of BiologyUniversity of Costa RicaSan JoseCosta Rica
  2. 2.Neuroscience Research CenterUniversity of Costa RicaSan JoseCosta Rica
  3. 3.Institute of BiochemistryFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  4. 4.Institute of Human GeneticsFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  5. 5.Neurology DepartmentHospital San Juan de DiosSan JoseCosta Rica

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