title: SCA27 caused by a chromosome translocation: further delineation of the phenotype.
abstract: We report of a spinocerebellar ataxia (SCA)27 in a daughter and her mother whose karyotype is 46, XX t(5;13)(q31.2;q33.1). The translocation breakpoint is identical in both patients, disrupting the gene-encoding fibroblast growth factor 14 isoform b (FGF14-1b). Clinically, both show signs of SCA, although the daughter is the most affected with early onset cerebellar ataxia, microcephaly, and severe mental retardation. FGF14-1b is the predominant isoform in brain, where it interacts with the voltage gated Na channel. Fgf14(-/-) mice develop ataxia and paroxysmal dyskinesia and have cognitive deficits. One missense and one non-sense mutation in FGF14 have previously been linked to SCA27. Truncation of one allele in our patients suggests that haploinsuffiency of FGF14 can cause SCA27.
authors.affiliation: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Misceo
authors.forename: M
authors.initials: M
authors.lastname: Fannemel
authors.forename: T
authors.initials: T
authors.lastname: Barøy
authors.forename: R
authors.initials: R
authors.lastname: Roberto
authors.forename: B
authors.initials: B
authors.lastname: Tvedt
authors.forename: T
authors.initials: T
authors.lastname: Jaeger
authors.forename: V
authors.initials: V
authors.lastname: Bryn
authors.forename: P
authors.initials: P
authors.lastname: Strømme
authors.forename: E
authors.initials: E
authors.lastname: Frengen
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13; D002895:Chromosomes, Human, Pair 5; D005346:Fibroblast Growth Factors / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000503:physiopathology; D014178:Translocation, Genetic
chemical_list: D020033:Protein Isoforms; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors