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Shasha Lu, MD, PhD; Chen Zhao, MD, PhD; Kanxing Zhao, MD, PhD; Ningdong Li, MD, PhD; Catharina Larsson, MD, PhD

Arch Ophthalmol. 2008;126(3):388-394.

Objective  To characterize the disease-causing mutations and associated clinical phenotypes in 5 Chinese families with congenital fibrosis of the extraocular muscles (CFEOM).

Methods  Ophthalmic investigations included visual acuity, levator function, documentation of compensatory head position, ocular motility, and slitlamp and fundus examinations. The kinesin family member 21A gene (KIF21A) was sequenced for mutation detection. Genotyping and linkage analysis were performed for the KIF21A/FEOM1 and FEOM3 loci.

Results  Four families were clinically classified as having CFEOM type 1 (CFEOM1) with full expression of severe ptosis and ophthalmoplegia. One family had CFEOM type 3 (CFEOM3) with typically varying expression of phenotypes between individuals. Recurrent heterozygous KIF21A mutations were identified in 2 CFEOM1 families (2860C>T) and the CFEOM3 family (2861G>A). In another CFEOM1 family, a novel missense mutation (84C>G, C28W) was revealed.

Conclusions  The novel KIF21A mutation 84C>G demonstrated in a CFEOM1 family affects the kinesin motor domain, supporting that mutations may also occur outside the commonly involved coiled-coil domain. The 2861G>A mutation found in a CFEOM3 family has been previously reported in CFEOM1, further supporting that different phenotypes can arise from identical mutations.

Clinical Relevance  Clinical and genetic characterization are complementary tools for diagnostic, prognostic, and treatment purposes in CFEOM.

Author Affiliations: Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital–Solna, Stockholm, Sweden (Drs Lu, C. Zhao, and Larsson); JiangSu Province Hospital, Nanjing, JiangSu (Dr Lu), and Laboratory of Molecular Genetics, Tianjin Eye Hospital, Tianjin Medical University, Tianjin (Drs C. Zhao, K. Zhao, and Li), People's Republic of China.

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