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dc.contributor.authorKaya, Namik-
dc.contributor.authorAlsagob, Maysoon-
dc.contributor.authorD'Adamo, Maria Cristina-
dc.contributor.authorAl-Bakheet, Albandary Bandary-
dc.contributor.authorHasan, Sonia M.-
dc.contributor.authorMuccioli, Maria-
dc.contributor.authorAlmutairi, Faten B.-
dc.contributor.authorAlmass, Rawan-
dc.contributor.authorAldosary, Mazhor S.-
dc.contributor.authorMonies, Dorota Marta-
dc.contributor.authorMustafa, Osama M.-
dc.contributor.authorAlyounes, Banan-
dc.contributor.authorKenana, Rosan-
dc.contributor.authorAl-Zahrani, Jawaher-
dc.contributor.authorNaim, Ewa A.-
dc.contributor.authorBinhumaid, Faisal S.-
dc.contributor.authorQari, Alya A.-
dc.contributor.authorAlmutairi, Fatema-
dc.contributor.authorMeyer, Brian Francis-
dc.contributor.authorPlageman, Timothy F.-
dc.contributor.authorPessia, Mauro-
dc.contributor.authorColak, Dilek-
dc.contributor.authorAl-Owain, Mohammed A.-
dc.date.accessioned2018-03-26T09:48:24Z-
dc.date.available2018-03-26T09:48:24Z-
dc.date.issued2016-
dc.identifier.citationKaya, N., Alsagob, M., D'Adamo, M. C., Al-Bakheet, A., Hasan, S., Muccioli, M.,... Al-Owain, M. (2016). KCNA4 deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disability. Journal of Medical Genetics, 53(11), 786-792.en_GB
dc.identifier.urihttps://www.um.edu.mt/library/oar//handle/123456789/28242-
dc.descriptionThis research was conducted through intramural funds provided by King Faisal Specialist Hospital and Research Centre (KFSHRC-RAC: 2120022) and National Plan for Science, Technology and Innovation Programme under King Abdulaziz City for Science and Technology (NSTIP/KACST) for supporting NK (11-BIO2221-20) and DC (11-BIO2072-20).en_GB
dc.description.abstractBackground Voltage-gated potassium channels are highly diverse proteins representing the most complex class of voltage-gated ion channels from structural and functional perspectives. Deficiency of these channels usually results in various human disorders. Objectives To describe a novel autosomal recessive syndrome associated with KCNA4 deficiency leading to congenital cataract, abnormal striatum, intellectual disability and attention deficit hyperactivity disorder. Methods We used SNP arrays, linkage analyses, autozygosity mapping, whole-exome sequencing, RT-PCR and two-electrode voltage-clamp recording. Results We identified a missense variant (p. Arg89Gln) in KCNA4 in four patients from a consanguineous family manifesting a novel syndrome of congenital cataract, abnormal striatum, intellectual disability and attention deficit hyperactivity disorder. The variant was fully segregated with the disease and absent in 747 ethnically matched exomes. Xenopus oocytes were injected with human Kv1.4 wild-type mRNA, R89Q and WT/R89Q channels. The wild type had mean current amplitude that was significantly greater than those recorded from the cells expressing the same amount of mutant mRNA. Co-expression of the wild type and mutant mRNAs resulted in mean current amplitude that was significantly different from that of the wild type. RTPCR indicated that KCNA4 is present in mouse brain, lens and retina. KCNA4 interacts with several molecules including synaptotagmin I, DLG1 and DLG2. The channel co-localises with cholinergic amacrine and rod bipolar cells in rats and is widely distributed in the central nervous system. Based on previous studies, the channel is highly expressed in outer retina, rod inner segments, hippocampus and concentrated in axonal membranes. Conclusion KCNA4 (Kv1.4) is implicated in a novel syndrome characterised by striatal thinning, congenital cataract and attention deficit hyperactivity disorder. Our study highlights potassium channels' role in ocular and neuronal genetics.en_GB
dc.language.isoenen_GB
dc.publisherBMJ Publishing Groupen_GB
dc.rightsinfo:eu-repo/semantics/restrictedAccessen_GB
dc.subjectPotassium channelsen_GB
dc.subjectMessenger RNAen_GB
dc.subjectMental fatigueen_GB
dc.titleKCNA4 deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disabilityen_GB
dc.typearticleen_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder.en_GB
dc.description.reviewedpeer-revieweden_GB
dc.identifier.doi10.1136/jmedgenet-2015-103637-
dc.publication.titleJournal of Medical Geneticsen_GB
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