Publications by authors named "H Alkuraya"
Background: Founder variants are ancestral variants shared by individuals who are not closely related. The large effect size of some of these variants in the context of Mendelian disorders offers numerous precision medicine opportunities.
Methods: Using one of the largest datasets on Mendelian disorders in the Middle East, we identified 2,908 medically relevant founder variants derived from 18,360 exomes and genomes and investigated their contribution to the clinical annotation of the human genome.
Article Synopsis
- Long-read whole genome sequencing (lrWGS) shows promise for diagnosing autosomal recessive diseases that exome sequencing fails to identify, as tested on a cohort of 34 families.
- In this study, likely causal variants were found in 13 families (38%), revealing novel candidate genes linked to conditions like neonatal lactic acidosis and neurodevelopmental disorders.
- The results indicate that while lrWGS can uncover complex genetic factors, there are still important interpretation challenges that need to be addressed to fully leverage this technology for genetic diagnosis.
Further delineation of HIDEA syndrome.
Am J Med Genet A
December 2020
Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in P4HTM, which encodes an atypical member of the prolyl 4-hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole-exome sequencing (WES) revealed novel disease-causing variants in P4HTM. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment/developmental delay, and hypotonia, which seem to be consistent findings.
View Article and Find Full Text PDFPurpose: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.
Methods: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.