title: Recurrent mutation in the crystallin alpha A gene associated with inherited paediatric cataract.
abstract: BACKGROUND
  Cataract is a major cause of childhood blindness worldwide. The purpose of this study was to determine the genetic cause of paediatric cataract in a South Australian family with a bilateral lamellar paediatric cataract displaying variable phenotypes.
  
  
  METHODS
  Fifty-one genes implicated in congenital cataract in human or mouse were sequenced in an affected individual from an Australian (Caucasian) family using a custom Ampliseq library on the Ion Torrent Personal Genome Machine. Reads were mapped against the human genome (hg19) and variants called with the Torrent Suite software. Variants were annotated to dbSNP 137 using Ion Reporter (IR 1.6.2) and were prioritised for validation if they were novel or rare and were predicted to be protein changing. We identified a previously reported oligomerization disrupting mutation, c.62G > A (p.R21Q), in the Crystallin alpha A (CRYAA) gene segregating in this three generation family. No other novel or rare coding mutations were detected in the known cataract genes sequenced. Microsatellite markers were used to compare the haplotypes between the family reported here and a previously published family with the same segregating mutation. Haplotype analysis indicated a potential common ancestry between the two South Australian families with this mutation. The work strengthens the genotype-phenotype correlations between this functional mutation in the crystallin alpha A (CRYAA) gene and paediatric cataract.
  
  
  CONCLUSIONS
  The p.R21Q mutation is the most likely cause of paediatric cataract in this family. The recurrence of this mutation in paediatric cataract families is likely due to a familial relationship.
authors: Department of Ophthalmology, School of Medicine, Flinders Medical Centre, Flinders University, Rm 4D 111.1, Flinders Dr, Bedford Park, Adelaide, 5042, Australia. shahra_80@yahoo.com.
authors: Shari
authors: S
authors: Javadiyan
authors: Department of Ophthalmology, School of Medicine, Flinders Medical Centre, Flinders University, Rm 4D 111.1, Flinders Dr, Bedford Park, Adelaide, 5042, Australia. jamie.craig@flinders.edu.au.
authors: Jamie E
authors: JE
authors: Craig
authors: Department of Ophthalmology, School of Medicine, Flinders Medical Centre, Flinders University, Rm 4D 111.1, Flinders Dr, Bedford Park, Adelaide, 5042, Australia. Emmanuelle.Souzeau@flinders.edu.au.
authors: Emmanuelle
authors: E
authors: Souzeau
authors: Department of Ophthalmology, School of Medicine, Flinders Medical Centre, Flinders University, Rm 4D 111.1, Flinders Dr, Bedford Park, Adelaide, 5042, Australia. shiwani.sharma@flinders.edu.au.
authors: Shiwani
authors: S
authors: Sharma
authors: Department of Haematology and Genetic Pathology, School of Medicine, Flinders University, Adelaide, Australia. karen.lower@flinders.edu.au.
authors: Karen M
authors: KM
authors: Lower
authors: Ophthalmology Department, Women's and Children's Hospital, Adelaide, Australia. john.pater@health.sa.gov.au.
authors: John
authors: J
authors: Pater
authors: Ophthalmology Department, Women's and Children's Hospital, Adelaide, Australia. TCasey@theresacasey.com.au.
authors: Theresa
authors: T
authors: Casey
authors: Mt Gambier Eye Centre, Mt Gambier, SA, Australia. doctiny@bigpond.com.
authors: Trevor
authors: T
authors: Hodson
authors: Department of Ophthalmology, School of Medicine, Flinders Medical Centre, Flinders University, Rm 4D 111.1, Flinders Dr, Bedford Park, Adelaide, 5042, Australia. kathryn.burdon@utas.edu.au.|Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. kathryn.burdon@utas.edu.au.
authors: Kathryn P
authors: KP
authors: Burdon
mesh_terms: D000293:Adolescent; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D038201:alpha-Crystallins / Q000737:chemistry / Q000235:genetics*
chemical_list: D038201:alpha-Crystallins