Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by 
short stature, brachydactyly, joint stiffness, and characteristic eye anomalies 
including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. 
Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance 
have been described and a gene for AR WMS has recently been mapped to chromosome 
19p13.3-p13.2. Here, we report on the exclusion of chromosome 19p13.3-p13.2 in a 
large AD WMS family and show that, despite clinical homogeneity, AD and AR WMS 
are genetically heterogeneous entities. Because two AD WMS families were 
consistent with linkage to chromosome 15q21.1, the fibrillin-1 gene was 
sequenced and a 24 nt in frame deletion within a latent transforming growth 
factor-beta1 binding protein (LTBP) motif of the fibrillin-1 gene was found in a 
AD WMS family (exon 41, 5074_5097del). This in frame deletion cosegregated with 
the disease and was not found in 186 controls. This study strongly suggests that 
AD WMS and Marfan syndrome are allelic conditions at the fibrillin-1 locus and 
adds to the remarkable clinical heterogeneity of type I fibrillinopathies.