F. Tanaka et al., Tissue-specific somatic mosaicism in spinal and bulbar muscular atrophy isdependent on CAG-repeat length and androgen receptor-gene expression level, AM J HU GEN, 65(4), 1999, pp. 966-973
Citations number
25
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
The factors influencing the tissue-specific pattern of somatic mosaicism in
GAG-repeat diseases have not yet been fully resolved. We performed a detai
led analysis of the degree of somatic mosaicism in various tissues from 20
patients with spinal and bulbar muscular atrophy (SBMA), including 4 who we
re deceased. The most outstanding feature was the prominent somatic mosaici
sm observed in the cardiac and skeletal muscles, composed predominantly of
postmitotic cells, and in the skin, prostate, and testis. The CNS tissues,
liver, and spleen showed the least mosaicism. The tissue distribution of so
matic mosaicism in patients with SBMA was markedly different from that in p
atients with Huntington disease (HD) and from that in patients with dentato
rubral-pallidoluysian atrophy (DRPLA). The degree of somatic mosaicism corr
elated with the GAG-repeat number but not with age at examination. Furtherm
ore, tissues with a higher mosaicism level corresponded well to those with
a higher expression Level of androgen receptor protein. The tissue-specific
pattern of somatic mosaicism related not only to cell composition with dif
ferent cell turnover rates but to repeat size and gene expression levels, a
nd postnatal cell division is unlikely to be a major cause of somatic mosai
cism probably because of the relative stability of CAG repeat in SBMA.