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.

The mutation specific for myotonic dystrophy (DM) is an unstable expanded CTG repeat located in the 3'-untranslated region of the myotonin protein kinase gene. Expansion of the CTG repeat shows a positive correlation with the severity of the disease and increases in successive generations of DM patients. Children with the congenital form of DM show the most severe phenotype and have large expansions, usually > 1000 repeats. For pregnant women with DM, prenatal diagnosis of DM may be offered. To reduce the time between chorionic villus sampling or amniocentesis and final results of DNA analysis in these cases, a fast and efficient method has been developed. This method combines direct PCR analyses for normal alleles with a nested PCR system followed by non-radioactive hybridization with a single-stranded probe.