PURPOSE: 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.
PURPOSE: 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: Kamron Khan; Adam Rudkin; David A Parry; Kathryn P Burdon; Martin McKibbin; Clare V Logan; Zakia I A Abdelhamed; James S Muecke; Narcis Fernandez-Fuentes; Kate J Laurie; Mike Shires; Rhys Fogarty; Ian M Carr; James A Poulter; Joanne E Morgan; Moin D Mohamed; Hussain Jafri; Yasmin Raashid; Ngy Meng; Horm Piseth; Carmel Toomes; Robert J Casson; Graham R Taylor; Michael Hammerton; Eamonn Sheridan; Colin A Johnson; Chris F Inglehearn; Jamie E Craig; Manir Ali Journal: Am J Hum Genet Date: 2011-09-09 Impact factor: 11.025
Authors: Evangelia S Panagiotou; Narcis Fernandez-Fuentes; Layal Abi Farraj; Martin McKibbin; Nursel H Elçioglu; Hussain Jafri; Eren Cerman; David A Parry; Clare V Logan; Colin A Johnson; Chris F Inglehearn; Carmel Toomes; Manir Ali Journal: Mol Vis Date: 2022-05-17 Impact factor: 2.711
Authors: Kamron Khan; Clare V Logan; Martin McKibbin; Eamonn Sheridan; Nursel H Elçioglu; Ozlem Yenice; David A Parry; Narcis Fernandez-Fuentes; Zakia I A Abdelhamed; Ahmed Al-Maskari; James A Poulter; Moin D Mohamed; Ian M Carr; Joanne E Morgan; Hussain Jafri; Yasmin Raashid; Graham R Taylor; Colin A Johnson; Chris F Inglehearn; Carmel Toomes; Manir Ali Journal: Hum Mol Genet Date: 2011-11-07 Impact factor: 6.150
Authors: Giuseppina Covello; Fernando J Rossello; Michele Filosi; Felipe Gajardo; Anne-Laure Duchemin; Beatrice F Tremonti; Michael Eichenlaub; Jose M Polo; David Powell; John Ngai; Miguel L Allende; Enrico Domenici; Mirana Ramialison; Lucia Poggi Journal: FASEB Bioadv Date: 2020-06-27