Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3)

Koki Yamada, Wai Man Chan, Caroline Andrews, Thomas Bosley, Emin C. Sener, Johan T. Zwaan, Paul B. Mullaney, Banu T. Öztürk, A. Nurten Akarsu, Louise J. Sabol, Joseph L. Demer, Timothy J. Sullivan, Irene Gottlob, Peter Roggenkäemper, David A. Mackey, Clara E. De Uzcategui, Nicolas Uzcategui, Bruria Ben-Zeev, Elias I. Traboulsi, Adriano MagliTeresa De Berardinis, Vincenzo Gagliardi, Sudha Awasthi-Patney, Marlene C. Vogel, Joseph F. Rizzo, Elizabeth C. Engle

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2218-2223
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

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Pedigree
Mutation
Phenotype
Congenital Fibrosis of the Extraocular Muscles
Databases
Information Storage and Retrieval
Strabismus
Genes
Fibrosis of Extraocular Muscles, Congenital, 3B
Incidence

ASJC Scopus subject areas

  • Ophthalmology

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Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). / Yamada, Koki; Chan, Wai Man; Andrews, Caroline; Bosley, Thomas; Sener, Emin C.; Zwaan, Johan T.; Mullaney, Paul B.; Öztürk, Banu T.; Akarsu, A. Nurten; Sabol, Louise J.; Demer, Joseph L.; Sullivan, Timothy J.; Gottlob, Irene; Roggenkäemper, Peter; Mackey, David A.; De Uzcategui, Clara E.; Uzcategui, Nicolas; Ben-Zeev, Bruria; Traboulsi, Elias I.; Magli, Adriano; De Berardinis, Teresa; Gagliardi, Vincenzo; Awasthi-Patney, Sudha; Vogel, Marlene C.; Rizzo, Joseph F.; Engle, Elizabeth C.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 7, 07.2004, p. 2218-2223.

Research output: Contribution to journalArticle

Yamada, K, Chan, WM, Andrews, C, Bosley, T, Sener, EC, Zwaan, JT, Mullaney, PB, Öztürk, BT, Akarsu, AN, Sabol, LJ, Demer, JL, Sullivan, TJ, Gottlob, I, Roggenkäemper, P, Mackey, DA, De Uzcategui, CE, Uzcategui, N, Ben-Zeev, B, Traboulsi, EI, Magli, A, De Berardinis, T, Gagliardi, V, Awasthi-Patney, S, Vogel, MC, Rizzo, JF & Engle, EC 2004, 'Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3)', Investigative Ophthalmology and Visual Science, vol. 45, no. 7, pp. 2218-2223. https://doi.org/10.1167/iovs.03-1413
Yamada, Koki ; Chan, Wai Man ; Andrews, Caroline ; Bosley, Thomas ; Sener, Emin C. ; Zwaan, Johan T. ; Mullaney, Paul B. ; Öztürk, Banu T. ; Akarsu, A. Nurten ; Sabol, Louise J. ; Demer, Joseph L. ; Sullivan, Timothy J. ; Gottlob, Irene ; Roggenkäemper, Peter ; Mackey, David A. ; De Uzcategui, Clara E. ; Uzcategui, Nicolas ; Ben-Zeev, Bruria ; Traboulsi, Elias I. ; Magli, Adriano ; De Berardinis, Teresa ; Gagliardi, Vincenzo ; Awasthi-Patney, Sudha ; Vogel, Marlene C. ; Rizzo, Joseph F. ; Engle, Elizabeth C. / Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). In: Investigative Ophthalmology and Visual Science. 2004 ; Vol. 45, No. 7. pp. 2218-2223.
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abstract = "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.",
author = "Koki Yamada and Chan, {Wai Man} and Caroline Andrews and Thomas Bosley and Sener, {Emin C.} and Zwaan, {Johan T.} and Mullaney, {Paul B.} and {\"O}zt{\"u}rk, {Banu T.} and Akarsu, {A. Nurten} and Sabol, {Louise J.} and Demer, {Joseph L.} and Sullivan, {Timothy J.} and Irene Gottlob and Peter Roggenk{\"a}emper and Mackey, {David A.} and {De Uzcategui}, {Clara E.} and Nicolas Uzcategui and Bruria Ben-Zeev and Traboulsi, {Elias I.} and Adriano Magli and {De Berardinis}, Teresa and Vincenzo Gagliardi and Sudha Awasthi-Patney and Vogel, {Marlene C.} and Rizzo, {Joseph F.} and Engle, {Elizabeth C.}",
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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

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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