Unraveling the genetic cause of hereditary ophthalmic disorders in Arab societies from Israel and the Palestinian Authority
Date
2020-01-02
Authors
Mayer, Anja K.
Balousha, Ghassan
Sharkia, Rajech
Mahajnah, Muhammad
Ayesh, Suhail
Schulze, Martin
Buchert, Rebecca
Zobor, Ditta
Azem, Abdussalam
Schols, Ludger
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group on behalf of the European Society of Human Genetics
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.