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Logo of bmcgeneBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genetics
 
BMC Genet. 2001; 2: 3.
Published online Feb 6, 2001. doi:  10.1186/1471-2156-2-3
PMCID: PMC29083
Analysis of human sarcospan as a candidate gene for CFEOM1
Kristine F O'Brien,1 Elizabeth C Engle,2,3 and Louis M Kunkelcorresponding author1,2,4
1Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
2Division of Genetics, Harvard Medical School, Boston, Massachusetts, USA
3Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
4Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
corresponding authorCorresponding author.
Kristine F O'Brien: kfobrien/at/mac.com; Elizabeth C Engle: engle/at/rascal.med.harvard.edu; Louis M Kunkel: kunkel/at/genetics.med.harvard.edu
Received December 21, 2000; Accepted February 6, 2001.
Abstract
Background
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is an autosomal dominant eye movement disorder linked to the pericentromere of chromosome 12 (12p11.2 - q12). Sarcospan is a member of the dystrophin associated protein complex in skeletal and extraocular muscle and maps to human chromosome 12p11.2. Mutations in the genes encoding each of the other components of the skeletal muscle sarcospan-sarcoglycan complex (α - δ sarcoglycan) have been shown to cause limb girdle muscular dystrophy (LGMD2C-F). To determine whether mutations in the sarcospan gene are responsible for CFEOM1 we: (1) attempted to map sarcospan to the CFEOM1 critical region; (2) developed a genomic primer set to directly sequence the sarcospan gene in CFEOM1 patients; and (3) generated an anti-sarcospan antibody to examine extraocular muscle biopsies from CFEOM1 patients.
Results
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.
Conclusions
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.
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