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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

Photographs of individual II:4 in pedigree XT. Photos are taken in primary gaze (E) and in the 8 cardinal gaze positions (A, B, C, D, F, G, H, and I). This subject demonstrates marked ophthalmoparesis, infraducted eyes in primary position, exotropia, and an inability to raise the eyes above midline. This patient also has bilateral ptosis (not shown).
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f1: Photographs of individual II:4 in pedigree XT. Photos are taken in primary gaze (E) and in the 8 cardinal gaze positions (A, B, C, D, F, G, H, and I). This subject demonstrates marked ophthalmoparesis, infraducted eyes in primary position, exotropia, and an inability to raise the eyes above midline. This patient also has bilateral ptosis (not shown).

Mentions: Family XT is from He Bei Province, China. All affected members shared the typical clinical features of CFEOM1 that have been reported previously in other ethnic families: congenital non-progressive ptosis, infraducted globe position in primary gaze, and upgaze and horizontal gaze palsy in both eyes. All patients including the proband, had evidence of aberrant innervation with nystagmoid movements in all directions of gaze. Forced duction testing of the superior rectus muscles and medial rectus muscles was positive (Figure 1 and Figure 2). Bell phenomenon was absent. Clinicopathological studies showed fibrotic extraocular muscles in the proband.


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)

Photographs of individual II:4 in pedigree XT. Photos are taken in primary gaze (E) and in the 8 cardinal gaze positions (A, B, C, D, F, G, H, and I). This subject demonstrates marked ophthalmoparesis, infraducted eyes in primary position, exotropia, and an inability to raise the eyes above midline. This patient also has bilateral ptosis (not shown).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Photographs of individual II:4 in pedigree XT. Photos are taken in primary gaze (E) and in the 8 cardinal gaze positions (A, B, C, D, F, G, H, and I). This subject demonstrates marked ophthalmoparesis, infraducted eyes in primary position, exotropia, and an inability to raise the eyes above midline. This patient also has bilateral ptosis (not shown).
Mentions: Family XT is from He Bei Province, China. All affected members shared the typical clinical features of CFEOM1 that have been reported previously in other ethnic families: congenital non-progressive ptosis, infraducted globe position in primary gaze, and upgaze and horizontal gaze palsy in both eyes. All patients including the proband, had evidence of aberrant innervation with nystagmoid movements in all directions of gaze. Forced duction testing of the superior rectus muscles and medial rectus muscles was positive (Figure 1 and Figure 2). Bell phenomenon was absent. Clinicopathological studies showed fibrotic extraocular muscles in the proband.

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