Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1

Chan, W. M. and Andrews, C. and Dragan, L. and Fredrick, D. and Armstrong, L. and Lyons, C. and Geraghty, M. T. and Hunter, D. G. and Yazdani, A. and Traboulsi, E. I. and Pott, J. W. R. and Gutowski, N. J. and Ellard, S. and Young, E. and Hanisch, F. and Koc, F. and Schnall, B. and Engle, E. C. (2007) Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1. BMC Genetics, 8.

[img] Text
Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1.pdf

Download (397kB)
[img] Text
1471-2156-8-26.pdf

Download (397kB)

Abstract

Background: Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids - Three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A. Results: Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands. Conclusion: Analysis ofsixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1. © 2007 Chan et al; licensee BioMed Central Ltd.

Item Type: Article
Additional Information: Cited By :41 Export Date: 16 February 2020 CODEN: BGMED Correspondence Address: Engle, E.C.; Program in Genomics, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, United States; email: elizabeth.engle@childrens.harvard.edu
Uncontrolled Keywords: kinesin protein KIF 21A unclassified drug KIF21A protein, human nerve protein amino acid substitution article autosomal dominant optic atrophy clinical article congenital fibrosis of the extraocular muscle type 1 congenital fibrosis of the extraocular muscle type 3 controlled study extraocular muscle gene mutation gene sequence genetic analysis genetic heterogeneity genetic screening genotype haplotype human nerve fiber transport nerve growth nucleotide sequence oculomotor nerve phenotype protein function strabismus amino acid sequence chemistry dominant gene female genetics inheritance male molecular genetics mutation pedigree protein tertiary structure Base Sequence DNA Mutational Analysis Genes, Dominant Humans Inheritance Patterns Molecular Sequence Data Nerve Tissue Proteins Protein Structure, Tertiary
Subjects: WW Ophthalmology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib7 lib7
Date Deposited: 04 May 2020 03:22
Last Modified: 04 May 2020 03:22
URI: http://eprints.mums.ac.ir/id/eprint/16955

Actions (login required)

View Item View Item