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Unraveling the genetic cause of hereditary ophthalmic disorders in Arab societies from Israel and the Palestinian Authority

European Journal of Human Genetics volume 28, pages 742–753 (2020)Cite this article

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Abstract

Visual impairment due to inherited ophthalmic disorders is amongst the most common disabilities observed in populations practicing consanguineous marriages. Here we investigated the molecular genetic basis of an unselected broad range of ophthalmic disorders in 20 consanguineous families from Arab villages of Israel and the Palestinian Authority. Most patients had little or very poor prior clinical workup and were recruited in a field study. Homozygosity mapping followed by candidate gene sequencing applying conventional Sanger sequencing or targeted next generation sequencing was performed in six families. In the remaining 14 families, one affected subject per family was chosen for whole exome sequencing. We discovered likely disease-causing variants, all homozygous, in 19 of 20 independent families (95%) including a previously reported novel disease gene for congenital nystagmus associated with foveal hypoplasia. Moreover, we found a family in which disease-causing variants for two collagenopathies — Stickler and Knobloch syndrome — segregate within a large sibship. Nine of the 19 distinct variants observed in this study were novel. Our study demonstrated a very high molecular diagnostic yield for a highly diverse spectrum of rare ophthalmic disorders in Arab patients from Israel and the Palestinian Authority, even with very limited prior clinical investigation. We conclude that ‘genetic testing first' may be an economic way to direct clinical care and to support proper genetic counseling and risk assessment in these families.

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Fig. 1: Pedigrees of all studied families.
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Acknowledgements

We are grateful to the patients and family members who participated in this study. Further, we are indebted to Dr. Ibrahim Yehya, the Scientific Director of the Triangle Regional Research and Development Center.

Funding

This work was supported by grants from the German Research Foundation (SCHO 754/5-2, WI 1189/8-2, and BA 2417/2-2) to LS, BW, and PB (principle applicants), and to GB, RS, SA, and AA (co-applicants). LS is a member of the European Network for Rare Neurological Diseases (Project ID No. 739510). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Anja K. Mayer & Martin Schulze

    Present address: Praxis fuer Humangenetik Tuebingen, Tuebingen, Germany

  2. Ludger Schöls

    Present address: German Center of Neurodegenerative Diseases (DZNE), Tuebingen, Germany

Authors and Affiliations

  1. Institute for Ophthalmic Research, Molecular Genetics Laboratory, Tuebingen, Germany

    Anja K. Mayer & Bernd Wissinger

  2. Department of Pathology and Histology, Al-Quds University, Eastern Jerusalem, Palestinian Authority, Jerusalem, Israel

    Ghassan Balousha

  3. The Triangle Regional Research and Development Center, Kfar Qari’, Israel

    Rajech Sharkia

  4. Beit-Berl Academic College, Beit-Berl, Israel

    Rajech Sharkia

  5. Child Neurology and Development Center, Hillel-Yaffe Medical Center, Hadera, Israel

    Muhammad Mahajnah

  6. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Muhammad Mahajnah

  7. Molecular Genetic Laboratory, Al-Makassed Islamic Charitable Society Hospital, Jerusalem, Israel

    Suhail Ayesh

  8. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany

    Martin Schulze, Rebecca Buchert & Peter Bauer

  9. University Eye Hospital, University of Tuebingen, Tuebingen, Germany

    Ditta Zobor

  10. The School of Neurobiology, Biochemistry and Biophysics, George S. Wise faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Abdussalam Azem

  11. Hertie Institute for Brain Research, University of Tuebingen, Tuebingen, Germany

    Ludger Schöls

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Mayer, A.K., Balousha, G., Sharkia, R. et al. Unraveling the genetic cause of hereditary ophthalmic disorders in Arab societies from Israel and the Palestinian Authority. Eur J Hum Genet 28, 742–753 (2020). https://doi.org/10.1038/s41431-019-0566-3

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