title: Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings.
abstract: OBJECTIVE
  Monogenic congenital cataract is one of the most genetically heterogeneous ocular conditions with almost 30 different genes involved in its etiology. In adult patients, genotype-phenotype correlations are troubled by eye surgery during infancy and/or long-term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency as the cause of autosomal recessive congenital cataract in a family from Costa Rica.
  
  
  METHODS
  Four affected siblings were included in the study. All of them underwent eye surgery during the first decade but medical records were not available. Congenital cataract was diagnosed by report. Molecular analysis included genome wide homozygosity mapping using a 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene.
  
  
  RESULTS
  Genome wide homozygosity mapping revealed a 6Mb region of homozygosity shared by two affected siblings at 17q25. The GALK1 gene was included in this interval and direct sequencing of this gene revealed a homozygous c.1144C>T mutation (p.Q382) in all four affected subjects.
  
  
  CONCLUSIONS
  This work demonstrates the utility of homozygosity mapping in the retrospective diagnosis of a family with congenital cataracts in which ocular surgery at early age, the lack of medical records, and the presence of long term eye complications, impeded a clear clinical diagnosis during the initial phases of evaluation.
authors.affiliation: Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Chacon-Camacho
authors.affiliation: Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Buentello-Volante
authors.affiliation: Cornea Department, "Dra. Olga Montoya" Ophthalmic Center, San Jose, Costa Rica.
authors.forename: Roberto
authors.initials: R
authors.lastname: Velázquez-Montoya
authors.affiliation: Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Raul
authors.initials: R
authors.lastname: Ayala-Ramirez
authors.affiliation: Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico; Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico. Electronic address: jczenteno@institutodeoftalmologia.org.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D000368:Aged; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005123:Eye; D005260:Female; D005686:Galactokinase / Q000172:deficiency / Q000235:genetics*; D005808:Genes, Recessive; D008040:Genetic Linkage / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods; D010375:Pedigree; D012189:Retrospective Studies; D035781:Siblings
chemical_list: C484715:GALK1 protein, human; D005686:Galactokinase
keywords: BRLMM; Bayesian Robust Linear Model with Mahalanobis distance classifier; C; Cataract; DNA; GALE; GALK1; GALT; Galactosemia; Homozygosity mapping; Mb; Ng; OMIM; On line Mendelian Inheritance in Man; PCR; Q; SNPs; T; UDP-galactose-4′-epimerase; cytosine; desoxyribonucleic acid; galactokinase; galactose-1-phosphate uridyltransferase; glutamine; megabase; nanogram; polymerase chain reaction; single nucleotide polymorphisms; thymine