KIF21A mutations in two Chinese families with congenital fibrosis of the extraocular muscles (CFEOM).

PURPOSE: Two Chinese families (XT and YT) with congenital fibrosis of the extraocular muscles (CFEOM) were identified. The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees. METHODS: Clinical characterization and genetic studies were performed. Microsatellite genotyping for linkage to the CFEOM1 and CFEOM3 loci was performed. The probands were screened for KIF21A mutations by bidirectional direct sequencing. Once a mutation was detected in the proband, all other participating family members and 100 unrelated control normal individuals were screened for the mutation. RESULTS: All affected individuals in family XT shared the common manifestations of CFEOM1. Family YT had two affected individuals, a mother and a daughter. The daughter had CFEOM1, while her mother never had congential ptosis but did have limited extraocular movements status post strabismus surgery. Haplotype analysis revealed that pedigree XT was linked to the 12q CFEOM1 locus and the affected memberes harbored the second most common missense mutation in KIF21A (2,861G>A, R954Q). Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W). Both of these mutations have been previously described. CONCLUSIONS: The observation of these two KIF21A mutations in a Chinese pedigree underscores the homogeneity of these mutations as a cause of CFEOM1 and CFEOM3 across ethnic divisions.

[Clinical investigation of the syndrome of congenital fibrosis of extraocular muscles].

OBJECTIVE: To analyze the clinical manifestations of congenital fibrosis of the extraocular muscles (CFEOM) both in their pedigrees and sporadic cases. METHODS: Six families and seven sporadic cases of CFEOM were retrospectively analyzed in the study. The clinical features including genetic characteristics, sex, age of first visit, major complains, subclassifications, features of ptosis and aberrant innervation were evaluated. RESULTS: The six families of CFEOM were autosomal dominant inherited traits and classified to the general fibrosis of the extraocular muscles with the inferior rectus muscles affected most severely. All patients except for 1 had binocular involvement. 2 out of the 29 affected members had ptosis and 7 had no aberrant innervation. The male-to-female ratio of the 7 sporadic cases was 2:5. 3 cases had monocular involvement. Among all the sporadic cases 3 cases were general fibrosis syndrome combined with inferior rectus fibrosis, 1 case was general fibrosis syndrome combined with superior rectus fibrosis, 3 cases were esotropia fixus. 1 patient had monocular ptosis while 4 patients had no ptosis. 5 patient had no aberrant innervation while the other two had. CONCLUSIONS: Clinically, the cases of CFEOM are relatively few but the clinical manifestations are complex. The combination of clinical characteristics and genetic analysis are the basis for the establishment of diagnosis. Further research is needed to understand the pathogenesis of the disease.