title: A Novel Single-Nucleotide Deletion (c.1020delA) in NSUN2 Causes Intellectual Disability in an Emirati Child.
abstract: Intellectual disability (ID) is a major public health burden on most societies with significant socioeconomic costs. It has been shown that genetic mutations in numerous genes are responsible for a proportion of hereditary forms of ID. NOP2/Sun transfer RNA (tRNA) methyltransferase family member 2 encoded by NSUN2 gene is a highly conserved protein and has been shown to cause autosomal recessive ID type 5 (MRT5). In this study, we recruited an Emirati consanguineous family with a patient diagnosed with ID. Whole-exome sequencing revealed a homozygous variant c.1020delA in NSUN2 gene. The variants segregated in an autosomal recessive mode of inheritance in the family. This variant is novel and causes a frameshift and premature stop codon. At the messenger RNA (mRNA) level, relative expression analysis showed a decreased level of NSUN2 mRNA in the affected child compared to a healthy individual. Mutation prediction analysis and clinical investigation confirmed the pathogenic nature of the identified variant. We therefore conclude that c.1020delA mutation in NSUN2 is most likely the cause of ID in our patient.
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. makanko.k@uaeu.ac.ae.
authors.forename: Makanko
authors.initials: M
authors.lastname: Komara
authors.affiliation: Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates. aishamsi@tawamhospital.ae.
authors.forename: Aisha M
authors.initials: AM
authors.lastname: Al-Shamsi
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. salma81bs@yahoo.fr.
authors.forename: Salma
authors.initials: S
authors.lastname: Ben-Salem
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. bassam.ali@uaeu.ac.ae.
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
authors.affiliation: Department of Pediatrics, College of Medicine and Heath Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates. l.algazali@uaeu.ac.ae.
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D018912:Arabs / Q000235:genetics; D001483:Base Sequence; D002653:Child Behavior Disorders / Q000235:genetics*; D018389:Codon, Nonsense; D003241:Consanguinity; D019175:DNA Methylation / Q000235:genetics; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017384:Sequence Deletion; D019892:eIF-2 Kinase / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D008780:Methyltransferases; C515610:NSUN2 protein, human; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase
keywords: Intellectual disability; NSUN2; UAE; tRNA methylation