title: Genetic heterogeneity for recessively inherited congenital cataract microcornea with corneal opacity.
abstract: OBJECTIVE
  To investigate whether three consanguineous families from the Punjab province of Pakistan, with affected members with recessively inherited congenital cataract microcornea with corneal opacity, are genetically homogeneous.
  
  
  METHODS
  An ophthalmic examination was performed on each family member to establish the diagnosis. The two largest families were analyzed by homozygosity mapping using SNP arrays. Linkage was confirmed using polymorphic microsatellite markers, and logarithm of odds (LOD) scores were calculated. Candidate genes were prioritized using the ENDEAVOUR program.
  
  
  RESULTS
  Autosomal recessive congenital cataract-microcornea with corneal opacity mapped to chromosome 10cen for family MEP57 and to either chromosomes 2ptel or 20p for family MEP60. For MEP57, the refined interval was 36.8 Mb flanked by D10S1208 (35.3 Mb) and D10S676 (72.1 Mb). For MEP60, the interval containing the mutation was either 6.7 Mb from the telomere of chromosome 2 to marker D2S281 or 3.8 Mb flanked by D20S906 (1.5 Mb) and D20S835 (5.3 Mb). Maximum multipoint LOD scores of 3.09, 1.94, and 3.09 were calculated at D10S567, D2S281, and D20S473 for families MEP57 and MEP60. Linkage to these loci was excluded for family MEP68. SLC4A11 was excluded as a candidate gene for the observed phenotype in MEP60.
  
  
  CONCLUSIONS
  The authors have identified two new loci, one on chromosome 10cen and the other on 2ptel or 20p, that are associated with recessively inherited congenital cataract-microcornea with corneal opacity. This phenotype is genetically heterogeneous in the Pakistani population. Further genetic studies of this kind, combined with a detailed phenotypic description, will contribute to more precise classification criteria for anterior segment disease.
authors.affiliation: Leeds Institute of Molecular Medicine, Leeds, United Kingdom.
authors.forename: Kamron
authors.initials: K
authors.lastname: Khan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Maskari
authors.forename: Martin
authors.initials: M
authors.lastname: McKibbin
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carr
authors.forename: Adam
authors.initials: A
authors.lastname: Booth
authors.forename: Moin
authors.initials: M
authors.lastname: Mohamed
authors.forename: Salina
authors.initials: S
authors.lastname: Siddiqui
authors.forename: James A
authors.initials: JA
authors.lastname: Poulter
authors.forename: David A
authors.initials: DA
authors.lastname: Parry
authors.forename: Clara V
authors.initials: CV
authors.lastname: Logan
authors.forename: Anwar
authors.initials: A
authors.lastname: Hashmi
authors.forename: Tehseen
authors.initials: T
authors.lastname: Sahi
authors.forename: Hussain
authors.initials: H
authors.lastname: Jafri
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Raashid
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Alex F
authors.initials: AF
authors.lastname: Markham
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Aine
authors.initials: A
authors.lastname: Rice
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000151:congenital / Q000235:genetics / Q000473:pathology; D002648:Child; D003315:Cornea / Q000473:pathology; D003316:Corneal Diseases / Q000151:congenital / Q000235:genetics / Q000473:pathology; D003318:Corneal Opacity / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D010154:Pakistan; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA