A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability.

Research paper by Megan D MD Louttit, Laura J LJ Kopplin, Robert P RP Igo, Jeremy R JR Fondran, Angela A Tagliaferri, David D Bardenstein, Anthony J AJ Aldave, Christopher R CR Croasdale, Marianne O MO Price, George O GO Rosenwasser, Jonathan H JH Lass, Sudha K SK Iyengar,

Indexed on: 03 Nov '11Published on: 03 Nov '11Published in: Cornea


To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD).Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry.Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness.Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

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