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Genetic basis of neurodevelopmental disorders in 103 Jordanian families |
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| Authors: | Tawfiq Froukh Omar Nafie Sana' A. S. Al Hait Lucia Laugwitz Julia Sommerfeld Marc Sturm Aya Baraghiti Tala Issa Anis Al-Nazer Philipp A. Koch Johannes Hanselmann Beate Kootz Peter Bauer Wael Al-Ameri Rami Abou Jamra Ayman J. Alfrook Moath Hamadallah Linda Sofan Angelika Riess Tobias B. Haack Olaf Riess Rebecca Buchert |
| Affiliation: | 1. Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan;2. Faculty of Medicine, Mutah University, Alkarak, Jordan;3. Private Clinic, Amman, Jordan;4. Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany;5. Ibn Alhytham Hospital, Amman, Jordan;6. Institute of Human Genetics, University Medical Center Leipzig, Leipzig, Germany;7. Farah Hospital, Amman, Jordan |
| Abstract: | We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability. |
| Keywords: | exome sequencing Jordan neurodevelopmental disorder PUS3 |