title: Mutation spectrum of Joubert syndrome and related disorders among Arabs.
abstract: Joubert syndrome (JS) is a rare autosomal recessive (AR), neurological condition characterized by dysgenesis of the cerebellar vermis with the radiological hallmark of molar tooth sign, oculomotor apraxia, recurrent hyperventilation and intellectual disability. Most cases display a broad spectrum of additional features, including polydactyly, retinal dystrophy and renal abnormalities, which define different subtypes of JS-related disorders (JSRDs). To date, 23 genes have been shown to cause JSRDs, and although most of the identified genes encode proteins involved in cilia function or assembly, the molecular mechanisms associated with ciliary signaling remain enigmatic. Arab populations are ethnically diverse with high levels of consanguinity (20-60%) and a high prevalence of AR disorders. In addition, isolated communities with very-high levels of inbreeding and founder mutations are common. In this article, we review the 70 families reported thus far with JS and JSRDs that have been studied at the molecular level from all the Arabic countries and compile the mutations found. We show that JS and the related JSRDs are genetically heterogeneous in Arabs, with 53 mutations in 15 genes. Thirteen of these mutations are potentially founder mutations for the region.
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University , Al-Ain, United Arab Emirates.
authors.forename: Salma
authors.initials: S
authors.lastname: Ben-Salem
authors.affiliation: Department of Paediatrics, Tawam Hospital , Al-Ain, Al-Ain, United Arab Emirates.
authors.forename: Aisha M
authors.initials: AM
authors.lastname: Al-Shamsi
authors.affiliation: Neurogenetics Laboratory, Department of Neuroscience and Pediatrics, Howard Hughes Medical Institute, University of California , San Diego, CA, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University , Al-Ain, United Arab Emirates.
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
authors.affiliation: Department of Paediatrics, College of Medicine and Heath Sciences, United Arab Emirates University , Al-Ain, United Arab Emirates.
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali