A Mutation in the Fibroblast Growth Factor 14 Gene is Associated with Autosomal Dominant Cerebellar Ataxia [corrected]

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2002 Dec 19

PMID 12489043

Citations 117

Authors

John C Van Swieten

Esther Brusse

Bianca M de Graaf

Elmar Krieger

Raoul van de Graaf

Inge de Koning

Anneke Maat-Kievit

Peter Leegwater

Dennis Dooijes

Ben A Oostra

Peter Heutink

Affiliations

Soon will be listed here.

Abstract

Hereditary spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders for which >/=14 different genetic loci have been identified. In some SCA types, expanded tri- or pentanucleotide repeats have been identified, and the length of these expansions correlates with the age at onset and with the severity of the clinical phenotype. In several other SCA types, no genetic defect has yet been identified. We describe a large, three-generation family with early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia, not associated with any of the known SCA loci, and a mutation in the fibroblast growth factor 14 (FGF14) gene on chromosome 13q34. Our observations are in accordance with the occurrence of ataxia and paroxysmal dyskinesia in Fgf14-knockout mice. As indicated by protein modeling, the amino acid change from phenylalanine to serine at position 145 is predicted to reduce the stability of the protein. The present FGF14 mutation represents a novel gene defect involved in the neurodegeneration of cerebellum and basal ganglia.

Citing Articles

Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.

Pellerin D, Iruzubieta P, Xu I, Danzi M, Cortese A, Synofzik M Curr Neurol Neurosci Rep. 2025; 25(1):16.

PMID: 39820740 DOI: 10.1007/s11910-024-01400-8.

The GAA repeat expansion is a major cause of ataxia in the Cypriot population.

Livanos I, Votsi C, Michailidou K, Pellerin D, Brais B, Zuchner S Brain Commun. 2025; 7(1):fcae479.

PMID: 39801711 PMC: 11724429. DOI: 10.1093/braincomms/fcae479.

The First Case of Autosomal Recessive Cerebellar Ataxia with Prominent Paroxysmal Non-kinesigenic Dyskinesia Caused by a Truncating FGF14 Variant in a Turkish Patient.

Turkdogan D, Smolina N, Tekgul S, Gul T, Yesilyurt A, Houlden H Mov Disord. 2024; 40(2):370-375.

PMID: 39704271 PMC: 11835525. DOI: 10.1002/mds.30087.

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Mohren L, Erdlenbruch F, Leitao E, Kilpert F, Hones G, Kaya S Nat Commun. 2024; 15(1):7665.

PMID: 39227614 PMC: 11372089. DOI: 10.1038/s41467-024-52148-1.

The evolving spectrum of complex inherited neuropathies.

Rossor A, Haddad S, Reilly M Curr Opin Neurol. 2024; 37(5):427-444.

PMID: 39083076 PMC: 11377048. DOI: 10.1097/WCO.0000000000001307.

References

Kelley L, MacCallum R, STERNBERG M . Enhanced genome annotation using structural profiles in the program 3D-PSSM. J Mol Biol. 2000; 299(2):499-520. DOI: 10.1006/jmbi.2000.3741. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Munoz-Sanjuan I, Smallwood P, Nathans J . Isoform diversity among fibroblast growth factor homologous factors is generated by alternative promoter usage and differential splicing. J Biol Chem. 2000; 275(4):2589-97. DOI: 10.1074/jbc.275.4.2589. View

. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000; 26(3):345-8. DOI: 10.1038/81664. View

Sobrido M, Cholfin J, Perlman S, Pulst S, Geschwind D . SCA8 repeat expansions in ataxia: a controversial association. Neurology. 2001; 57(7):1310-2. DOI: 10.1212/wnl.57.7.1310. View

Hecht H, Adar R, Hofmann B, Bogin O, Weich H, Yayon A . Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces. Acta Crystallogr D Biol Crystallogr. 2001; 57(Pt 3):378-84. DOI: 10.1107/s0907444900020813. View

Nakamura K, Jeong S, Uchihara T, Anno M, Nagashima K, Nagashima T . SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001; 10(14):1441-8. DOI: 10.1093/hmg/10.14.1441. View

Smallwood P, Munoz-Sanjuan I, Tong P, Macke J, Hendry S, Gilbert D . Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development. Proc Natl Acad Sci U S A. 1996; 93(18):9850-7. PMC: 38518. DOI: 10.1073/pnas.93.18.9850. View

Juvonen V, Hietala M, Paivarinta M, Rantamaki M, Hakamies L, Kaakkola S . Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion. Ann Neurol. 2000; 48(3):354-61. View

10.

Koob M, Moseley M, Schut L, Benzow K, Bird T, Day J . An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet. 1999; 21(4):379-84. DOI: 10.1038/7710. View

11.

Ornitz D, Itoh N . Fibroblast growth factors. Genome Biol. 2001; 2(3):REVIEWS3005. PMC: 138918. DOI: 10.1186/gb-2001-2-3-reviews3005. View

12.

Hooft R, Vriend G, Sander C, Abola E . Errors in protein structures. Nature. 1996; 381(6580):272. DOI: 10.1038/381272a0. View

13.

Zoghbi H, Orr H . Polyglutamine diseases: protein cleavage and aggregation. Curr Opin Neurobiol. 1999; 9(5):566-70. DOI: 10.1016/S0959-4388(99)00013-6. View

14.

Matsuura T, Yamagata T, Burgess D, Rasmussen A, Grewal R, Watase K . Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet. 2000; 26(2):191-4. DOI: 10.1038/79911. View

15.

Wang Q, Bardgett M, Wong M, Wozniak D, Lou J, McNeil B . Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14. Neuron. 2002; 35(1):25-38. DOI: 10.1016/s0896-6273(02)00744-4. View

16.

OHearn E, Holmes S, Calvert P, Ross C, Margolis R . SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion. Neurology. 2001; 56(3):299-303. DOI: 10.1212/wnl.56.3.299. View

17.

Rasmussen A, Matsuura T, Ruano L, Yescas P, Ochoa A, Ashizawa T . Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol. 2001; 50(2):234-9. DOI: 10.1002/ana.1081. View

18.

Gwinn-Hardy K, Chen J, Liu H, Liu T, Boss M, Seltzer W . Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese. Neurology. 2000; 55(6):800-5. DOI: 10.1212/wnl.55.6.800. View

19.

Vriend G . WHAT IF: a molecular modeling and drug design program. J Mol Graph. 1990; 8(1):52-6, 29. DOI: 10.1016/0263-7855(90)80070-v. View

20.

Rost B . Twilight zone of protein sequence alignments. Protein Eng. 1999; 12(2):85-94. DOI: 10.1093/protein/12.2.85. View