TY - JOUR
T1 - Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3)
AU - Yamada, Koki
AU - Chan, Wai Man
AU - Andrews, Caroline
AU - Bosley, Thomas M.
AU - Sener, Emin C.
AU - Zwaan, Johan T.
AU - Mullaney, Paul B.
AU - Öztürk, Banu T.
AU - Akarsu, A. Nurten
AU - Sabol, Louise J.
AU - Demer, Joseph L.
AU - Sullivan, Timothy J.
AU - Gottlob, Irene
AU - Roggenkäemper, Peter
AU - Mackey, David A.
AU - De Uzcategui, Clara E.
AU - Uzcategui, Nicolas
AU - Ben-Zeev, Bruria
AU - Traboulsi, Elias I.
AU - Magli, Adriano
AU - De Berardinis, Teresa
AU - Gagliardi, Vincenzo
AU - Awasthi-Patney, Sudha
AU - Vogel, Marlene C.
AU - Rizzo, Joseph F.
AU - Engle, Elizabeth C.
PY - 2004/7
Y1 - 2004/7
N2 - PURPOSE. Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G→A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C→T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype.
AB - PURPOSE. Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G→A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C→T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype.
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U2 - 10.1167/iovs.03-1413
DO - 10.1167/iovs.03-1413
M3 - Article
C2 - 15223798
AN - SCOPUS:3142654134
SN - 0146-0404
VL - 45
SP - 2218
EP - 2223
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 7
ER -