SCA27 caused by a chromosome translocation: further delineation of the phenotype.
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.
Misceo
D
D
Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway.
Fannemel
M
M
Barøy
T
T
Roberto
R
R
Tvedt
B
B
Jaeger
T
T
Bryn
V
V
Strømme
P
P
Frengen
E
E
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
D020033:Protein Isoforms; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors