CLINICAL AND LINKAGE STUDY OF A LARGE FAMILY WITH SIMPLE ECTOPIA LENTIS LINKED TO FBN1

Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. (C) 1994 Wiley-Liss, Inc.