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Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability

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Abstract

Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.

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Acknowledgment

We thank the families for their kind participation. This work was supported by QBRI, Hamad Bin Khalifa University (member of Qatar Foundation) and by Jordan University of Science and Technology.

Details of the contribution of individual authors

AA designed the study, analyzed data, and wrote manuscript; SA recruited patients, made full clinical assessment; WH done the experimental work, IT done the bioinformatics analysis. All authors reviewed and corrected the manuscript.

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Authors and Affiliations

  1. Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, P.O. Box 5825, Qatar

    Asem M. Alkhateeb, Wesal Habbab & I. Richard Thompson

  2. Biotechnology and Genetics Department, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Asem M. Alkhateeb

  3. Neurosciences Department, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Samah K. Aburahma

Authors
  1. Asem M. Alkhateeb
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  2. Samah K. Aburahma
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  3. Wesal Habbab
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  4. I. Richard Thompson
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Correspondence to Asem M. Alkhateeb.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

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Authors declare no conflict of interest.

Additional information

Synopsis : Novel mutations in WWOX, RARS2 and C10orf2 exemplify the uniqueness of the population studied and represent new mechanisms of protein disruption and disease.

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Alkhateeb, A.M., Aburahma, S.K., Habbab, W. et al. Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability. Metab Brain Dis 31, 901–907 (2016). https://doi.org/10.1007/s11011-016-9827-9

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