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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

Sequence chromatographs of Family XT (A, B) and YT (C, D). The sequence of the unaffected member is normal (A, C), the affected patient with CFEOM harbor the heterozygous KIF21A mutation 2861G>A (B) and 2860C>T (D), respectively.
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f6: Sequence chromatographs of Family XT (A, B) and YT (C, D). The sequence of the unaffected member is normal (A, C), the affected patient with CFEOM harbor the heterozygous KIF21A mutation 2861G>A (B) and 2860C>T (D), respectively.

Mentions: Genetic analysis revealed probable linkage of the CFEOM1 phenotype in family XT to the KIF21A locus with a maximum lod score of 2.24 at D12S331 (theta=0, 100% penetrance). Linkage to the FEOM3 locus was ruled-out (Table 3, Figure 5). A missense heterozygous mutation in KIF21A was identified in this family: 2,861G>A (R954Q; Figure 6A,B). This mutation was detected in all affected and no affected family members and not in 100 control subjects.


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)

Sequence chromatographs of Family XT (A, B) and YT (C, D). The sequence of the unaffected member is normal (A, C), the affected patient with CFEOM harbor the heterozygous KIF21A mutation 2861G>A (B) and 2860C>T (D), respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Sequence chromatographs of Family XT (A, B) and YT (C, D). The sequence of the unaffected member is normal (A, C), the affected patient with CFEOM harbor the heterozygous KIF21A mutation 2861G>A (B) and 2860C>T (D), respectively.
Mentions: Genetic analysis revealed probable linkage of the CFEOM1 phenotype in family XT to the KIF21A locus with a maximum lod score of 2.24 at D12S331 (theta=0, 100% penetrance). Linkage to the FEOM3 locus was ruled-out (Table 3, Figure 5). A missense heterozygous mutation in KIF21A was identified in this family: 2,861G>A (R954Q; Figure 6A,B). This mutation was detected in all affected and no affected family members and not in 100 control subjects.

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