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METAP1 mutation is a novel candidate for autosomal recessive intellectual disability

Journal of Human Genetics volume 66, pages 215–218 (2021)Cite this article

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Abstract

Intellectual disability (ID) is a genetic and clinically heterogeneous common disease and underlying molecular pathogenesis can frequently not be identified by whole-exome/genome testing. Here, we report four siblings born to a consanguineous union who presented with intellectual disability and discuss the METAP1 pathway as a novel etiology of ID. Genomic analyses demonstrated that patients harbor a novel homozygous nonsense mutation in the gene METAP1. METAP1 codes for methionine aminopeptidase 1 (MetAP1) which oversees the co-translational excision of the first methionine remnants in eukaryotes. The loss-of-function mutations to this gene may result in a defect in the translation of many essential proteins within a cell. Improper neuronal function resulting from this loss of essential proteins could lead to neurologic impairment and ID.

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Acknowledgements

The authors thank the reported family for participating in this study

Funding

This work was supported by the Yale Program on Neurogenetics and Yale Center for Mendelian Genomics. The Yale Center for Mendelian Genomics (UM1HG006504) is funded by the National Human Genome Research Institute. The GSP Coordinating Center (U24HG008956) contributed to cross-program scientific initiatives and provided logistical and general study coordination. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey

    Ahmet Okay Caglayan

  2. Department of Pediatrics, School of Medicine, Dicle University, 21060, Diyarbakir, Turkey

    Fesih Aktar

  3. Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT, 06510, USA

    Kaya Bilguvar

  4. Department of Neurosurgery, Neurobiology and Genetics, New Haven, CT, 06520-8082, USA

    Jacob F. Baranoski, Gozde Tugce Akgumus, Akdes Serin Harmanci, Emine Zeynep Erson-Omay, Katsuhito Yasuno & Murat Gunel

  5. Division of Pediatric Neurology and Genetics, Department of Pediatrics, Meram Medical Faculty, Necmettin Erbakan University, 42080, Konya, Turkey

    Huseyin Caksen

Authors
  1. Ahmet Okay Caglayan
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  2. Fesih Aktar
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  3. Kaya Bilguvar
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  4. Jacob F. Baranoski
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  5. Gozde Tugce Akgumus
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  8. Katsuhito Yasuno
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  9. Huseyin Caksen
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  10. Murat Gunel
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Contributions

AOC, KB, and MG designed the study. AOC analyzed the exome data. AOC and KB performed linkage analysis. AOC, JFB, and GTA performed sanger sequencing, AOC, FA, HC, and MG participated in ascertaining the patients and families and worked on the neurological and clinical investigation on the patients. KY wrote the in-house data analysis exome pipeline, EZEO run the pipeline. ASH analyzed the exome CNV data. AOC analyzed co-expression data. AOC wrote the paper.

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Correspondence to Ahmet Okay Caglayan.

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Caglayan, A.O., Aktar, F., Bilguvar, K. et al. METAP1 mutation is a novel candidate for autosomal recessive intellectual disability. J Hum Genet 66, 215–218 (2021). https://doi.org/10.1038/s10038-020-0820-0

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  • DOI: https://doi.org/10.1038/s10038-020-0820-0

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