Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13

A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implic ated in functions as diverse as blood coagulation, activation of complement , and determination of cell fate during development. The gene for one such protein, S1-5, was identified from a subtractively enriched cDNA library fr om a patient with Werner syndrome and was shown to be preferentially expres sed in senescent and quiescent fibroblasts. We have cloned and characterize d. in human and mouse. a novel gene that shows significant homology to the gene for S1-5. We have determined that the encoded protein contains four EG F domains and six calcium-binding EGF domains. On the basis of its homology to known proteins, we have designated this gene EFEMP2 (Egf-containing fib ulin-like extracellular matrix protein 2) and the gene for the S1-5 protein EFEMP1. Like EFEMP1, this novel gene is expressed in a wide range of adult and fetal tissues. In contrast to EFEMP1, however, EFEMP2 is not significa ntly overexpressed in senescent or quiescent fibroblasts, suggesting a dive rsity of function within this new EGF-like domain subfamily. We have mapped EFEMP2 to 11q13, in an area where several retinopathies have been genetica lly linked. Given that mutations in EFEMP1 have been recently described in patients with Doyne honeycomb retinal dystrophy, EFEMP2 becomes a good cand idate for such disorders.