title: Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin.
abstract: OBJECTIVE
  The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract.
  
  
  METHODS
  Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products.
  
  
  RESULTS
  A maximum two-point lod score of 6.37 at theta=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5'-untranslated region (5'-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects.
  
  
  CONCLUSIONS
  The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.
authors.affiliation: Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India. vanita_kumar@yahoo.com
authors.forename: Vanita
authors.initials: V
authors.lastname: Vanita
authors.forename: James Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Guleria
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Daljit
authors.initials: D
authors.lastname: Singh
authors.forename: Karl
authors.initials: K
authors.lastname: Sperling
authors.forename: Jai Rup
authors.initials: JR
authors.lastname: Singh
mesh_terms: D020121:5' Untranslated Regions; D000225:Adenine; D001052:Apoferritins; D002386:Cataract / Q000097:blood / Q000209:etiology*; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D017124:Conserved Sequence; D005260:Female; D005293:Ferritins / Q000097:blood; D008040:Genetic Linkage; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D007194:India; D007907:Lens Nucleus, Crystalline / Q000002:abnormalities*; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D020218:Response Elements; D013577:Syndrome
chemical_list: D020121:5' Untranslated Regions; C507433:FTL protein, human; D010455:Peptides; D006147:Guanine; D005293:Ferritins; D001052:Apoferritins; D000225:Adenine