Dataset Information

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

ABSTRACT: 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.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.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.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.

SUBMITTER: Yang X

PROVIDER: S-EPMC2965570 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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

Yang Xian X Yamada Koki K Katz Bradley B Guan Hongzai H Wang Lifei L Andrews Caroline C Zhao Guiqiu G Engle Elizabeth C EC Chen Haoyu H Tong Zongzhong Z Kong Jie J Hu Cong C Kong Qinglan Q Fan Guiyun G Wang Ze Z Ning Meizhen M Zhang Shaoyan S Xu Jinling J Zhang Kang K

Molecular vision 20101013

<h4>Purpose</h4>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.<h4>Methods</h4>Clinical characterization and genetic studies were performed. Microsatellite genotyping for linkage to the CFEOM1 and CFEOM3 loci was performed. The probands were screened for ...[more]

PMID: 21042561

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Project description:Orbital magnetic resonance imaging (MRI) was used to investigate the structural basis of motility abnormalities in congenital fibrosis of the extraocular muscles type 3 (CFEOM3), a disorder resulting from missense mutations in TUBB3, which encodes neuron-specific beta-tubulin isotype III.Ophthalmic examinations in 13 volunteers from four CFEOM3 pedigrees and normal control subjects, were correlated with TUBB3 mutation and MRI findings that demonstrated extraocular muscle (EOM) size, location, contractility, and innervation.Volunteers included clinically affected and clinically unaffected carriers of R262C and D417N TUBB3 amino acid substitutions and one unaffected, mutation-negative family member. Subjects with CFEOM3 frequently had asymmetrical blepharoptosis, limited vertical duction, variable ophthalmoplegia, exotropia, and paradoxical abduction in infraduction. MRI demonstrated variable, asymmetrical levator palpebrae superioris and superior rectus EOM atrophy that correlated with blepharoptosis, deficient supraduction, and small orbital motor nerves. Additional EOMs exhibited variable hypoplasia that correlated with duction deficit, but the superior oblique muscle was spared. Ophthalmoplegia occurred only when the subarachnoid width of CN3 was <1.9 mm. A-pattern exotropia was frequent, correlating with apparent lateral rectus (LR) muscle misinnervation by CN3. Optic nerve (ON) cross sections were subnormal, but rectus pulley locations were normal.CFEOM3 caused by TUBB3 R262C and D417N amino acid substitutions features abnormalities of EOM innervation and function that correlate with subarachnoid CN3 hypoplasia, occasional abducens nerve hypoplasia, and subclinical ON hypoplasia that can resemble CFEOM1. Clinical and MRI findings in CFEOM3 are more variable than those in CFEOM1 and are often asymmetrical. Apparent LR innervation by the inferior rectus motor nerve is an overlapping feature of Duane retraction syndrome and CFEOM1. These findings suggest that CFEOM3 is an asymmetrical, variably penetrant, congenital cranial dysinnervation disorder leading to secondary EOM atrophy.

Dataset Information

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

Publications

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

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