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 tendancy 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.

Keywords

Affiliated Institutions

• Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes FR
• Centre National de la Recherche Scientifique FR
• Hôpital Pellegrin FR
• Inserm FR
• Hôpital Cardiologique du Haut-Lévêque FR

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