title: Autosomal recessive congenital cataract in consanguineous Pakistani families is associated with mutations in GALK1.
abstract: OBJECTIVE
  To identify the pathogenic mutations responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
  
  
  METHODS
  All affected individuals underwent detailed ophthalmologic and medical examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was performed with polymorphic microsatellite markers on genomic DNA from affected and unaffected family members and logarithm of odds (LOD) scores were calculated. All coding exons of galactokinase (GALK1) were sequenced to identify pathogenic lesions.
  
  
  RESULTS
  Clinical records and ophthalmological examinations suggested that affected individuals have nuclear cataracts. Linkage analysis localized the critical interval to chromosome 17q with a maximum LOD score of 5.54 at theta=0, with D17S785 in family PKCC030. Sequencing of GALK1, a gene present in the critical interval, identified a single base pair deletion: c.410delG, which results in a frame shift leading to a premature termination of GALK1: p.G137fsX27. Additionally, we identified a missense mutation: c.416T>C, in family PKCC055 that results in substitution of a leucine residue at position 139 with a proline residue: p.L139P, and is predicted to be deleterious to the native GALK1 structure.
  
  
  CONCLUSIONS
  Here, we report pathogenic mutations in GALK1 that are responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Afshan
authors.initials: A
authors.lastname: Yasmeen
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Haiba
authors.initials: H
authors.lastname: Kaul
authors.forename: Sadia
authors.initials: S
authors.lastname: Mohsin
authors.forename: Mohsin
authors.initials: M
authors.lastname: Khan
authors.forename: Zaheeruddin A
authors.initials: ZA
authors.lastname: Qazi
authors.forename: Idrees A
authors.initials: IA
authors.lastname: Nasir
authors.forename: Ahmad U
authors.initials: AU
authors.lastname: Zafar
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005686:Galactokinase / Q000737:chemistry / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: C484715:GALK1 protein, human; D005686:Galactokinase
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