Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias

Abstract

The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a group of neurodegenerative disorders with overlapping as well as highly variable phenotypes. Genetically, at least 25 different loci have been identified. Seven SCAs are caused by CAG trinucleotide repeat expansions, for 13 the chromosomal localization is known solely. Recently, a missense mutation in the fibroblast growth factor 14 gene (FGF14) has been reported in a Dutch family with a new dominantly inherited form of SCA. To evaluate the frequency of mutations in the FGF14 gene, we performed molecular genetic analyses for the five exons in 208 nonrelated familial ataxia cases and 208 control samples. In one patient, we detected a novel single base pair deletion in exon 4 (c.487delA) creating a frameshift mutation. In addition, we found DNA polymorphisms in exon 1a, 4, and 5, an amino-acid exchange at position 124, as well as a single-nucleotide polymorphism in the 3 0 -untranslated region of exon 5.

Functional evolutionary history of the mouse Fgf gene family

“…FGF20 is a potential risk factor for Parkinson's disease (van der Walt et al, 2004;Satake et al, 2007). FGF13 is a candidate gene for Börjeson-Forssman-Lehmann syndrome (Gecz et al, 1999) and a hereditary spinocerebellar ataxia syndrome (SCA27) is caused by mutations in FGF14 (van Swieten et al, 2003;Dalski et al, 2005).…”

Fibroblast growth factor homologous factors: Evolution, structure, and function

“…In humans, spinocerebellar ataxia (SCA) is a genetically inherited syndrome, and many different SCA loci have been genetically mapped. One SCA locus spans the FHF4 gene, and coding missense or frameshift mutations have been identified in a few families transmitting SCA (Dalski et al, 2005;van Swieten et al, 2003). The third Fhf4 −/− phenotype is muscle weakness, as manifested by reduced ability to hang on to tilted or inverted grids and reduced climbing ability.…”

Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families

“…Point mutations may result in decreased stability of the proteins, and frameshift mutations in truncated proteins (Van Swieten et al 2003;Dalski et al 2005). More recently, single nucleotide substitutions have been identified in the puratrophin-1 and contactin 4 (CNTN4) genes, classified as 16q-linked ADCA and SCA16 respectively (Takashima et al 2001;Li et al 2003;Mizusawa et al 2004;Ishikawa et al 2005;Miura et al 2006).…”