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

Yang X, Yamada K, Katz B, Guan H, Wang L, Andrews C, Zhao G, Engle EC, Chen H, Tong Z, Kong J, Hu C, Kong Q, Fan G, Wang Z, Ning M, Zhang S, Xu J, Zhang K - Mol. Vis. (2010)

Bottom Line: Family YT had two affected individuals, a mother and a daughter.Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W).Both of these mutations have been previously described.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Medical College of Qingdao University, the Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong Province, China. yangxian_70@yahoo.com.cn

ABSTRACT

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.

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Related in: MedlinePlus

Pedigree and haplotype analysis of Family YT at the FEOM1 and FEOM3 loci. Black symbols identify clinically affected individuals. Genotyping data and schematic haplotype bars for FEOM1 markers (A) and FEOM3 markers (B) are shown below the symbol for each individual. The black bars denote the potential disease-associated alleles. The white bars indicate the inheritance of non disease-associated haplotypes.
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f7: Pedigree and haplotype analysis of Family YT at the FEOM1 and FEOM3 loci. Black symbols identify clinically affected individuals. Genotyping data and schematic haplotype bars for FEOM1 markers (A) and FEOM3 markers (B) are shown below the symbol for each individual. The black bars denote the potential disease-associated alleles. The white bars indicate the inheritance of non disease-associated haplotypes.

Mentions: Linkage could not be established in Family YT because only two individuals were affected. However, haplotype data were used to determine co-inheritance of the CFEOM phenotype with the FEOM1 and FEOM3 loci (Figure 7). Sequence analysis of three coding exons in KIF21A revealed a missense de novo heterozygous mutation (2,860C>T, R954W) in affected individuals II:1 and III:1 (Figure 6C,D). The remaining family members did not harbor the mutation, including I:1. Thus, the mutation arose de novo in II:1 on the allele she inherited from her father. Others have also reported the occurance of de novo KIF21A mutations on the paternal allele [13].


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

Yang X, Yamada K, Katz B, Guan H, Wang L, Andrews C, Zhao G, Engle EC, Chen H, Tong Z, Kong J, Hu C, Kong Q, Fan G, Wang Z, Ning M, Zhang S, Xu J, Zhang K - Mol. Vis. (2010)

Pedigree and haplotype analysis of Family YT at the FEOM1 and FEOM3 loci. Black symbols identify clinically affected individuals. Genotyping data and schematic haplotype bars for FEOM1 markers (A) and FEOM3 markers (B) are shown below the symbol for each individual. The black bars denote the potential disease-associated alleles. The white bars indicate the inheritance of non disease-associated haplotypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965570&req=5

f7: Pedigree and haplotype analysis of Family YT at the FEOM1 and FEOM3 loci. Black symbols identify clinically affected individuals. Genotyping data and schematic haplotype bars for FEOM1 markers (A) and FEOM3 markers (B) are shown below the symbol for each individual. The black bars denote the potential disease-associated alleles. The white bars indicate the inheritance of non disease-associated haplotypes.
Mentions: Linkage could not be established in Family YT because only two individuals were affected. However, haplotype data were used to determine co-inheritance of the CFEOM phenotype with the FEOM1 and FEOM3 loci (Figure 7). Sequence analysis of three coding exons in KIF21A revealed a missense de novo heterozygous mutation (2,860C>T, R954W) in affected individuals II:1 and III:1 (Figure 6C,D). The remaining family members did not harbor the mutation, including I:1. Thus, the mutation arose de novo in II:1 on the allele she inherited from her father. Others have also reported the occurance of de novo KIF21A mutations on the paternal allele [13].

Bottom Line: Family YT had two affected individuals, a mother and a daughter.Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W).Both of these mutations have been previously described.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Medical College of Qingdao University, the Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong Province, China. yangxian_70@yahoo.com.cn

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus