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A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia

Received: 12 January 2018     Accepted: 29 January 2018     Published: 5 May 2018
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Abstract

Mutations in ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) lead to autosomal recessive periventricular heterotopia (PH). To date, 11 mutations, (six missense mutations, one splicing mutation, one small deletion, two small insertions, and one small deletion/insertion) have been reported. Assessing ARFGEF2 mutations will provide a holistic overview of PH. This retrospective study was conducted in 2016 at King Faisal Specialist Hospital and Research Center. For the index patient, magnetic resonance imaging studies revealed a symmetrical focal hyperintensity involving the putamen bilaterally and the inner aspect of the globus pallidus. After family members were genotyped, an autozygosity analysis was performed, followed by exome sequencing of the index patient; A comprehensive filtering approach based on the loss of heterozygosity (LOH) was used to identify variants in phenotypically relevant genes. We report a consanguineous family with two affected individuals, a boy and a girl, with a history of microcephaly, global developmental delay, intellectual disability, myoclonic seizure, and dystonia. The patients carried a novel nonsense mutation (c.3974G>A, p. Trp1325*) in the Armadillo-type fold domain of ARFGEF2. These findings extend our understanding of the phenotype–genotype correlations for ARFGEF2 mutations.

Published in International Journal of Genetics and Genomics (Volume 6, Issue 1)
DOI 10.11648/j.ijgg.20180601.13
Page(s) 11-17
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2018. Published by Science Publishing Group

Keywords

Developmental Delay, ARFGEF2, Intellectual Disability, Myoclonic Seizure, Dystonia, Periventricular Heterotopia

References
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Cite This Article
  • APA Style

    Lina Al Neghery, Rosan Kenana, Albandary Al Bakheet, Rawan Al Mass, Faten Al Mutairi, et al. (2018). A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia. International Journal of Genetics and Genomics, 6(1), 11-17. https://doi.org/10.11648/j.ijgg.20180601.13

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    ACS Style

    Lina Al Neghery; Rosan Kenana; Albandary Al Bakheet; Rawan Al Mass; Faten Al Mutairi, et al. A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia. Int. J. Genet. Genomics 2018, 6(1), 11-17. doi: 10.11648/j.ijgg.20180601.13

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    AMA Style

    Lina Al Neghery, Rosan Kenana, Albandary Al Bakheet, Rawan Al Mass, Faten Al Mutairi, et al. A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia. Int J Genet Genomics. 2018;6(1):11-17. doi: 10.11648/j.ijgg.20180601.13

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  • @article{10.11648/j.ijgg.20180601.13,
      author = {Lina Al Neghery and Rosan Kenana and Albandary Al Bakheet and Rawan Al Mass and Faten Al Mutairi and Maysoon Al Sagob and Aliya Qari and Rozeena Huma and Dilek Colak and Maha Daghestani and Namik Kaya and Moeenaldeen Al Sayed},
      title = {A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia},
      journal = {International Journal of Genetics and Genomics},
      volume = {6},
      number = {1},
      pages = {11-17},
      doi = {10.11648/j.ijgg.20180601.13},
      url = {https://doi.org/10.11648/j.ijgg.20180601.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20180601.13},
      abstract = {Mutations in ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) lead to autosomal recessive periventricular heterotopia (PH). To date, 11 mutations, (six missense mutations, one splicing mutation, one small deletion, two small insertions, and one small deletion/insertion) have been reported. Assessing ARFGEF2 mutations will provide a holistic overview of PH. This retrospective study was conducted in 2016 at King Faisal Specialist Hospital and Research Center. For the index patient, magnetic resonance imaging studies revealed a symmetrical focal hyperintensity involving the putamen bilaterally and the inner aspect of the globus pallidus. After family members were genotyped, an autozygosity analysis was performed, followed by exome sequencing of the index patient; A comprehensive filtering approach based on the loss of heterozygosity (LOH) was used to identify variants in phenotypically relevant genes. We report a consanguineous family with two affected individuals, a boy and a girl, with a history of microcephaly, global developmental delay, intellectual disability, myoclonic seizure, and dystonia. The patients carried a novel nonsense mutation (c.3974G>A, p. Trp1325*) in the Armadillo-type fold domain of ARFGEF2. These findings extend our understanding of the phenotype–genotype correlations for ARFGEF2 mutations.},
     year = {2018}
    }
    

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    T1  - A Systematic Genetic Assessment of ARFGEF2 Mutations in Periventricular Heterotopia
    AU  - Lina Al Neghery
    AU  - Rosan Kenana
    AU  - Albandary Al Bakheet
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    AU  - Aliya Qari
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    JF  - International Journal of Genetics and Genomics
    JO  - International Journal of Genetics and Genomics
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    PB  - Science Publishing Group
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    AB  - Mutations in ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) lead to autosomal recessive periventricular heterotopia (PH). To date, 11 mutations, (six missense mutations, one splicing mutation, one small deletion, two small insertions, and one small deletion/insertion) have been reported. Assessing ARFGEF2 mutations will provide a holistic overview of PH. This retrospective study was conducted in 2016 at King Faisal Specialist Hospital and Research Center. For the index patient, magnetic resonance imaging studies revealed a symmetrical focal hyperintensity involving the putamen bilaterally and the inner aspect of the globus pallidus. After family members were genotyped, an autozygosity analysis was performed, followed by exome sequencing of the index patient; A comprehensive filtering approach based on the loss of heterozygosity (LOH) was used to identify variants in phenotypically relevant genes. We report a consanguineous family with two affected individuals, a boy and a girl, with a history of microcephaly, global developmental delay, intellectual disability, myoclonic seizure, and dystonia. The patients carried a novel nonsense mutation (c.3974G>A, p. Trp1325*) in the Armadillo-type fold domain of ARFGEF2. These findings extend our understanding of the phenotype–genotype correlations for ARFGEF2 mutations.
    VL  - 6
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Author Information
  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia

  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

  • Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

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