G130V, a common FRDA point mutation, appears to have arisen from a common founder

• Published in: Human genetics Vol. 105; no. 4; pp. 343 - 346
• Main Authors: DELATYCKI, M. B, KNIGHT, M, KOENIG, M, COSSEE, M, WILLIAMSON, R, FORREST, S. M
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.10.1999; Berlin; New York, NY
• Subjects: Adaptor Proteins, Signal Transducing; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Founder Effect; Friedreich Ataxia - genetics; Haplotypes; Humans; Male; Medical sciences; Minisatellite Repeats; Nerve Tissue Proteins - genetics; Neurology; Pedigree; Point Mutation; Trinucleotide Repeats; Human; Nervous system diseases; Family study; Founder effect; Cerebral disorder; Genetic disease; Phenotype; Frataxin; Central nervous system disease; Point mutation; Genetics; Degenerative disease; Friedreich ataxia; Spinal cord disease; Haplotype
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390051112

Friedreich ataxia (FRDA) is the most common inherited ataxia. About 98% of mutant alleles have an expansion of a GAA trinucleotide repeat in intron 1 of the affected gene, FRDA. The other 2% are point mutations. Of the 17 point mutations so far described, three appear to be more common. One of these is the G130V mutation in exon 4 of FRDA. G130V, when present with an expanded GAA repeat on the other allele, is associated with an atypical FRDA phenotype. Haplotype analysis was undertaken on the four families who have been described with this mutation. The results suggest a common founder for this mutation. Although marked differences in extragenic marker haplotypes were seen in one family, similar intragenic haplotyping suggests the same mutation founder for this family with the differences explicable by two recombination events.