Analysis of human sarcospan as a candidate gene for CFEOM1

When tested by polymerase chain reaction, sarcospan sequence was not detected on yeast or bacterial artificial chromosomes from the CFEOM1 critical region. Sequencing of the sarcospan gene in CFEOM1 patients from 6 families revealed no mutations. Immunohistochemical studies of CFEOM1 extraocular muscles showed normal levels of sarcospan at the membrane. Finally, sarcospan was electronically mapped to bacterial artificial chromosomes that are considered to be outside of the CFEOM1 critical region.In this report we evaluate sarcospan as a candidate gene for CFEOM1. We have found that it is highly unlikely that sarcospan is involved in the pathogenesis of this disease. As of yet no sarcospan gene mutations have been found to cause muscular abnormalities.CFEOM1 is an autosomal dominant disorder that has been linked to the pericentromere of chromosome 12, flanked by marker D12S1584 on the p arm and D12S1668 on the q arm [1, 2]. The clinical phenotype consists of congenital, bilateral ptosis and external ophthalmoplegia, with the eyes partially or completely fixed in a hypotrophic or downward position. On autopsy, CFEOM1 patients appear to be lacking the superior division of cranial nerve III, which innervates the levator and superior rectus muscles [3]. Whether this disease is caused by a primary defect in the nerve or the muscle remains unclear. The disease was initially linked to an 8 centiMorgan region spanning the centromere of chromosome 12, and then further refined to a critical region of 3 cM [1, 2]. Yeast and bacterial artificial chromosome (YAC and BAC) contigs have been generated and a positional cloning approach to identify the CFEOM1 causative gene is ongoing.Sarcospan is a member of the dystrophin associated protein complex present in skeletal and extraocular muscle [4,5,6]. Sarcospan is most tightly associated with the transmembrane sarcoglycan subcomplex, mutation of which causes autosomal recessive limb girdle muscular dystrophy (LGMD2C-2F) [7,8,9,10,11].