title: RGS6: a novel gene associated with congenital cataract, mental retardation, and microcephaly in a Tunisian family.
abstract: OBJECTIVE
  The object of this study is to identify the underlying genetic defect in a consanguineous Tunisian family affected with autosomal recessive congenital cataract associated with mental retardation and microcephaly.
  
  
  METHODS
  A whole-genome scan was performed with polymorphic microsatellites in the axiom data for the screened members. Homozygous regions were analyzed with integrated Systems Tool for Eye gene Discovery (iSyTE), to identify candidate genes with lens-enriched expression that were potentially associated with cataract. Then we screened for mutations by direct sequencing. Structure and function of the mutant gene were analyzed by bioinformatics analysis.
  
  
  RESULTS
  Using whole-genome scanning, we identified six runs of homozygosity shared among affected members of the studied family. Analysis of these regions by iSyTE allowed us to select 3 genes (RGS6, PCNX, and P4HA1) according to their expression in 3 critical stages of lens development. Upon screening for mutations by sequencing analysis, we found a novel mutation in RGS6, the splice-acceptor variant c.1369-1G>C that was not previously reported in congenital cataract phenotypes.
  
  
  CONCLUSIONS
  Our study identified a new gene to be included in the large spectrum of cataract-associated genes. Importantly, the study demonstrated that, in addition to lens-enriched genes that exhibit high expression levels, genes identified by iSyTE that are highly lens-enriched but have lower absolute expression may also represent candidates for potential function in the lens.
authors.affiliation: Laboratoire Génétique Humaine, Faculté Médecine de Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Manèl
authors.initials: M
authors.lastname: Chograni
authors.affiliation: King Faisal Specialist Hospital and Research Center, Developmental Genetics Unit, Riyad, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
authors.affiliation: Charles Nicolle Hospital, Congenital and Hereditary Disorders Department, Tunis, Tunisia.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Maazoul
authors.affiliation: Laboratoire Génétique Humaine, Faculté Médecine de Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Lariani
authors.affiliation: Laboratoire Génétique Humaine, Faculté Médecine de Tunis, University Tunis El Manar, Tunis, Tunisia Charles Nicolle Hospital, Congenital and Hereditary Disorders Department, Tunis, Tunisia.
authors.forename: Habiba
authors.initials: H
authors.lastname: Chaabouni-Bouhamed
mesh_terms: D000015:Abnormalities, Multiple; D002386:Cataract / Q000151:congenital / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000453:epidemiology / Q000235:genetics*; D008831:Microcephaly / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D014416:Tunisia / Q000453:epidemiology
chemical_list: D020710:RGS Proteins; C400194:RGS6 protein, human; D004247:DNA
keywords: congenital cataract; mental retardation; microcephaly