title: Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.
abstract: The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.
authors.affiliation: Laboratory of Human Genetics, Faculty of Medicine of Tunis, University Tunis ElManar, Tunis, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Chograni
authors.affiliation: Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, Riyad, Saudi Arabia.
authors.forename: F S
authors.initials: FS
authors.lastname: Alkuraya
authors.affiliation: Congenital and Hereditary Disorders Department, Charles Nicolle hospital, Tunis, Tunisia.
authors.forename: I
authors.initials: I
authors.lastname: Ourteni
authors.affiliation: Congenital and Hereditary Disorders Department, Charles Nicolle hospital, Tunis, Tunisia.
authors.forename: F
authors.initials: F
authors.lastname: Maazoul
authors.affiliation: Laboratory of Human Genetics, Faculty of Medicine of Tunis, University Tunis ElManar, Tunis, Tunisia.
authors.forename: I
authors.initials: I
authors.lastname: Lariani
authors.affiliation: Laboratory of Human Genetics, Faculty of Medicine of Tunis, University Tunis ElManar, Tunis, Tunisia.|Congenital and Hereditary Disorders Department, Charles Nicolle hospital, Tunis, Tunisia.
authors.forename: H B
authors.initials: HB
authors.lastname: Chaabouni
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000175:diagnosis* / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010641:Phenotype; D050765:Qa-SNARE Proteins / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D050765:Qa-SNARE Proteins
keywords: association; autosomal recessive; congenital cataract; genome scan; iSyTE analysis; intellectual disability