Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world

Annastiina Lund, Bjarne Udd, Vesa Juvonen, Peter M. Andersen, Kristina Cederquist, Mark Davis, Cinzia Gellera, Christina Kölmel, Lars Olof Ronnevi, Anne Dorte Sperfeld, Sven Asger Sörensen, Lisbeth Tranebjaerg, Lionel Van Maldergem, Mitsunori Watanabe, Markus Weber, Leone Yeung, Marja Liisa Savontaus

Research output: Contribution to journalArticle


SBMA (spinal and bulbar muscular atrophy), also called Kennedy disease, is an X-chromosomal recessive adult-onset neurodegenerative disorder caused by death of the spinal and bulbar motor neurones and dorsal root ganglia. Patients may also show signs of partial androgen insensitivity. SBMA is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene on the X-chromosome. Our previous study suggested that all the Nordic patients with SBMA originated from an ancient Nordic founder mutation, but the new intragenic SNP marker ARd12 revealed that the Danish patients derive their disease chromosome from another ancestor. In search of relationships between patients from different countries, we haplotyped altogether 123 SBMA families from different parts of the world for two intragenic markers and 16 microsatellites spanning 25 cM around the AR gene. The fact that different SBMA founder haplotypes were found in patients from around the world implies that the CAG repeat expansion mutation has not been a unique event. No expansion-prone haplotype could be detected. Trinucleotide diseases often show correlation between the repeat length and the severity and earlier onset of the disease. The longer the repeat, the more severe the symptoms are and the onset of the disease is earlier. A negative correlation between the CAG repeat length and the age of onset was found in the 95 SBMA patients with defined ages at onset.

Original languageEnglish
Pages (from-to)431-436
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number6
Publication statusPublished - 2001


  • CAG repeat disorder
  • Founder effect
  • Kennedy disease
  • SBMA
  • Trinucleotide repeat

ASJC Scopus subject areas

  • Genetics(clinical)

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    Lund, A., Udd, B., Juvonen, V., Andersen, P. M., Cederquist, K., Davis, M., Gellera, C., Kölmel, C., Ronnevi, L. O., Sperfeld, A. D., Sörensen, S. A., Tranebjaerg, L., Van Maldergem, L., Watanabe, M., Weber, M., Yeung, L., & Savontaus, M. L. (2001). Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world. European Journal of Human Genetics, 9(6), 431-436.