Identification of a novel SCA14 mutation in a Dutch autosomal dominant cerebellar ataxia family

Warrenburg, B.P.C. van de; Verbeek, Dineke S.; Piersma, Sytse J.; Hennekam, F. A. M.; Pearson, P. L.; Knoers, Nine V A M; Kremer, H.P.H.; Sinke, Richard J.

doi:10.1212/01.wnl.0000098883.79421.73

Cited by 94 publications

(89 citation statements)

References 29 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, point mutations in the genes for the protein kinase Cg (PRKCG) and the fibroblast growth factor 14 (FGF14) have been found to be associated with forms of ADCA. 1,2 FGF14 is a member of a subclass of fibroblast growth factors that is expressed in the developing and adult central nervous system. 3 The FGF14 gene is located at chromosome 13q34 and composed of five exons.…”

Section: Introductionmentioning

confidence: 99%

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

Dalski

Atici

Kreuz³

et al. 2004

Eur J Hum Genet

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Dalski

Atici

Kreuz³

et al. 2004

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Expansions of triplet or pentanucleotide repeat have been found to be the pathogenic mutations for several forms of ADCAs, including spinocerebellar ataxia type 1 (SCA1) (Orr et al 1993), SCA2 (Imbert et al 1996;Pulst et al 1996;Sanpei et al 1996), SCA3/Machado-Joseph disease (SCA3/MJD) (Kawaguchi et al 1994), SCA6 (Zhuchenko et al 1997), SCA7 , SCA10 (Matsuura et al 2000), SCA12 (Holmes et al 1999), SCA17 (Nakamura et al 2001), and DRPLA (Koide et al 1994;Nagafuchi et al 1994). More recently, point mutations in the protein kinase C gamma gene (PRKCG) have been proven to be pathogenic for SCA14 (van de Warrenburg et al 2003;Yabe et al 2003). Eight additional gene loci have also been mapped: SCA4 on 16q (Flanigan et al 1996), SCA5 on 11p (Ranum et al 1994), SCA11 on 15q (Worth et al 1999), SCA15 on 3p (Knight et al 2003), SCA16 on 8q (Miyoshi et al 2001), SCA19 on 1p (Verbeek et al 2002), SCA21 on 7p (Vuillaume et al 2002), SCA22 on 1p (Chung et al 2003), and SCA 25 on 2p (Stevanin et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

Shimizu¹,

Yoshida

Okano³

et al. 2004

J Hum Genet

View full text Add to dashboard Cite

The frequency of autosomal-dominant cerebellar ataxia (ADCA) subtypes was examined in 86 unrelated families originating from Nagano prefecture. In Nagano, the prevalence of spinocerebellar degeneration (SCD) was approximately 22 per 100,000 population. Among ADCA families, SCA6 was the most prevalent subtype (16 families, 19%), followed by DRPLA (nine families, 10%), SCA3/MJD (three families, 3%), SCA1 (two families, 2%), and SCA2 (one family, 1%). No families with SCA7, SCA12, or SCA17 were detected. Compared with other districts in Japan, the prevalence of SCA3/MJD was very low in Nagano. More interestingly, the ratio of genetically undetermined ADCA families was much higher in Nagano (55 families, 65%) than in other districts in Japan. These families tended to accumulate in geographically restricted areas such as Kiso, Saku, and Ina, indicating that the founder effect might be responsible for the high frequency of ADCA in these areas. Most patients clinically showed slowly progressive pure cerebellar ataxia of late-onset (ADCA III). In the case of 36 patients from 36 genetically undetermined ADCA III families, however, no one was completely consistent with the founder allele proposed for 16q-ADCA. These results indicate that there might be genetically distinct ADCA subtypes in Nagano.

show abstract

“…PCR products of exon 4 and intronic boundaries were screened for molecular (Chen et al , 2005van de Warrenburg et al 2003;Yabe et al 2003;Stevanin et al 2004;Verbeek et al 2005) variants by SSCP analysis (Orita et al 1989). Electrophoresis was carried out in 15% polyacrylamide gels at 15°C.…”

Section: Mutation Analysismentioning

confidence: 99%

A novel H101Q mutation causes PKCγ loss in spinocerebellar ataxia type 14

et al. 2005

View full text Add to dashboard Cite

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder, first described in a Japanese family, showing linkage to chromosome 19q13.4-qter. Recently, mutations have been identified in the PRKCG gene in families with SCA14. The PRKCG gene encodes the protein kinase Cc (PKCc), a member of a serine/threonine kinase family involved in signal transduction important for several cellular processes, including cell proliferation and synaptic transmission. To identify the disease-causing mutation in a large group of ataxia patients, we searched for mutations in the PRKCG gene. We ascertained 366 unrelated patients with spinocerebellar ataxia, either pure or with associated features such as epilepsy, mental retardation, seizures, paraplegia, and tremor. A C-to-G transversion in exon 4, resulting in a histidine-to-glutamine change at codon 101 of the PKCc protein, was identified in patients from a family with slowly progressive pure cerebellar ataxia. Functional studies performed in HEK293 cells transfected with normal or mutant construct showed that this mutation affects PKCc stability or solubility, verified by time-dependent decreased protein levels in cell culture. In conclusion, the H101Q mutation causes slowly progressive uncomplicated ataxia by interfering with PKCc stability or solubility, which consequently may cause in either case a decrease in the overall PKCc-dependent phosphorylation.

show abstract

Identification of a novel SCA14 mutation in a Dutch autosomal dominant cerebellar ataxia family

Abstract: A SCA-14-linked Dutch ADCA family with a novel missense mutation in the PRKCG gene was identified.

Cited by 94 publications

References 29 publications

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

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

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

A novel H101Q mutation causes PKCγ loss in spinocerebellar ataxia type 14

Contact Info

Product

Resources

About