| Summary: | <p>Abstract</p> <p>Background</p> <p>To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the <it>FEOM1</it> locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in <it>ARIX,</it> the CFEOM2 disease gene.</p> <p>Results</p> <p>Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to <it>FEOM1.</it> Two small CFEOM1 families were not linked to <it>FEOM1,</it> and both were consistent with linkage to <it>FEOM3.</it> We screened two CFEOM1 families consistent with linkage to <it>FEOM2</it> and 5 sporadic individuals with classic CFEOM and did not detect <it>ARIX</it> mutations.</p> <p>Conclusions</p> <p>The phenotype of two small CFEOM1 families does not map to <it>FEOM1,</it> establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the <it>FEOM3</it> gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified <it>ARIX</it> mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM.</p>
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