title: Moderate instability of the trinucleotide repeat in spino bulbar muscular atrophy.
abstract: Increased length of a protein-coding CAG repeat within the androgen receptor gene appears to be the only type of mutation responsible for spino-bulbal muscular atrophy (SBMA or Kennedy disease). We have analysed a large 4-generation SBMA family and found that the mutant allele was unstable upon transmission from parent to child, with a documented variation from 46 to 53 repeats and a tendency to increase in size (7 increases and a single decrease in 17 events), which appeared stronger upon transmission from a male than from a female. Our results suggest also limited somatic instability of the abnormal allele, with observable variation of up to 2-3 repeats. This indicates that the behavior of the CAG repeat is similar to that observed for small premutations in the fragile X syndrome, or small abnormal alleles in myotonic dystrophy, two diseases which are caused by expansion of an unstable trinucleotide repeat.
authors.affiliation: Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Strasbourg, France.
authors.forename: V
authors.initials: V
authors.lastname: Biancalana
authors.forename: F
authors.initials: F
authors.lastname: Serville
authors.forename: J
authors.initials: J
authors.lastname: Pommier
authors.forename: J
authors.initials: J
authors.lastname: Julien
authors.forename: A
authors.initials: A
authors.lastname: Hanauer
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005260:Female; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome
chemical_list: D009838:Oligodeoxyribonucleotides; D011944:Receptors, Androgen