The clinical manifestation and linkage analysis in one Chinese family with congenital fibrosis of extraocular muscles

Objective: To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscles and to identify the location of candidate gene of the disease in chromosome.

Methods: The clinical feature of all affected members in this family were examined. A genome-wide linkage screening was conducted. Direct genomic sequencing was used to evaluate the candidate gene KIf21A.

Results: Four affected members in the pedigree were born with classic phenotype of CFEOM. By linkage analysis the disease gene was mapped to chromosomal region 12p11.2-q12 defined by microsatellite markers D12S1648 and D12S1668. The maximum Lod Score was 2.12 (D12S1090). Direct sequence showed no mutation in all exons and exon-intron boundaries of the candidate gene KIF21A, a polymorphism substitution occurred in the exon 21.

Conclusions: The disorder in this family should be referred as CFEOM1 which was inherited as an autosomal dominant trait. The candidate gene was linked to CFEOM1 locus on chromosome 12p11.2-q12, between marker D12S1648 and D12S1668. It's more likely that KIf21A is not the disease causing gene in this family.