title: Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts.
abstract: OBJECTIVE
  The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree.
  
  
  METHODS
  All participating individuals underwent a detailed ophthalmic examination. Each patient's medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA. Genetic analysis was performed to rule out linkage to known arCC loci and genes. Whole-exome sequencing libraries were prepared and paired-end sequenced. A large deletion was found that segregated with arCC in the family, and chromosome walking was conducted to estimate the proximal and distal boundaries of the deletion mutation.
  
  
  RESULTS
  Exclusion and linkage analysis suggested linkage to a region of chromosome 6p24 harboring GCNT2 (glucosaminyl (N-acetyl) transferase 2) with a two-point logarithm of odds score of 5.78. PCR amplifications of the coding exons of GCNT2 failed in individuals with arCC, and whole-exome data analysis revealed a large deletion on chromosome 6p in the region harboring GCNT2. Chromosomal walking using multiple primer pairs delineated the extent of the deletion to approximately 190 kb. Interestingly, a failure to amplify a junctional fragment of the deletion break strongly suggests an insertion in addition to the large deletion.
  
  
  CONCLUSIONS
  Here, we report a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family.
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Irum
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Shahid Y
authors.initials: SY
authors.lastname: Khan
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Daud
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Firoz
authors.initials: F
authors.lastname: Kabir
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Rauf
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Fareeha
authors.initials: F
authors.lastname: Fatima
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Hira
authors.initials: H
authors.lastname: Iqbal
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Saif
authors.initials: S
authors.lastname: Al Obaisi
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Muhammad Asif
authors.initials: MA
authors.lastname: Naeem
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Idrees A
authors.initials: IA
authors.lastname: Nasir
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.|Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan.|National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.affiliation: Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan.|National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Allen O
authors.initials: AO
authors.lastname: Eghrari
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
mesh_terms: D000818:Animals; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D017349:N-Acetylhexosaminyltransferases / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: C106501:N-acetylglucosaminyltransferase IGnT; C000617996:GCNT2 protein, human; D017351:N-Acetylglucosaminyltransferases; D017349:N-Acetylhexosaminyltransferases