title: Mutation of the start codon in the FRDA1 gene: linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor.
abstract: Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA 1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG-->ATT (M11) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M11 mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.
authors.affiliation: Universität Lübeck, Institut für Humangenetik, Lübeck, Germany. zuehlke@medinf.mu-luebeck.de
authors.forename: C
authors.initials: C
authors.lastname: Zühlke
authors.forename: F
authors.initials: F
authors.lastname: Laccone
authors.forename: M
authors.initials: M
authors.lastname: Cossée
authors.forename: A
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: E
authors.initials: E
authors.lastname: Schwinger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002874:Chromosome Mapping; D018387:Codon, Initiator / Q000235:genetics*; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics*; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D018911:Trinucleotide Repeats
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018387:Codon, Initiator; D005819:Genetic Markers; D009419:Nerve Tissue Proteins