TY - JOUR
T1 - Mitotic and meiotic stability of the CAG repeat in the X-linked spinal and bulbar muscular atrophy gene
AU - Watanabe, M.
AU - Abe, K.
AU - Aoki, M.
AU - Yasuo, K.
AU - Itoyama, Y.
AU - Shoji, M.
AU - Ikeda, Y.
AU - Lizuka, T.
AU - Ikeda, M.
AU - Shizuka, M.
AU - Mizushima, K.
AU - Hirai, S.
PY - 1996/9
Y1 - 1996/9
N2 - X-linked spinal and bulbar muscular atrophy (SBMA) occurs due to an expansion of the trinucleotide repeat (CAG), in the androgen receptor gene. Anticipation is relatively rare in SBMA in contrast to spinocerebellar ataxia type 1 (SCA1), and dentatorubral and pallidoluysian atrophy (DRPLA) which show obvious paternal anticipation. The differences in the CAG repeat number were compared among sperm, leukocytes and skeletal muscles of SBMA patients. In SBMA, the sperm of most patients and the skeletal muscle of all patients showed the same repeat number as their leukocytes, whereas the increase in the repeat number from leukocytes to sperm was evident in SCA1 and DRPLA patients. The higher mosaicism level in sperm compared with leukocytes was common in SBMA, SCA1 and DRPLA, and the level of sperm was lower in SBMA than in SCA1 and DRPLA. Thus, spermatogenesis was suggested to be strongly associated with paternal anticipation. The mosaicism level was smaller in SBMA than in other (CAG), expanded disorders, and smallest in the SBMA carrier females. These findings demonstrate that the CAG repeat in SBMA is relatively stable in mitotic and meiotic processes, and there is a possibility that the lower mosaicism level of the carrier females compared with the SBMA patients is associated with X-linked recessive inheritance.
AB - X-linked spinal and bulbar muscular atrophy (SBMA) occurs due to an expansion of the trinucleotide repeat (CAG), in the androgen receptor gene. Anticipation is relatively rare in SBMA in contrast to spinocerebellar ataxia type 1 (SCA1), and dentatorubral and pallidoluysian atrophy (DRPLA) which show obvious paternal anticipation. The differences in the CAG repeat number were compared among sperm, leukocytes and skeletal muscles of SBMA patients. In SBMA, the sperm of most patients and the skeletal muscle of all patients showed the same repeat number as their leukocytes, whereas the increase in the repeat number from leukocytes to sperm was evident in SCA1 and DRPLA patients. The higher mosaicism level in sperm compared with leukocytes was common in SBMA, SCA1 and DRPLA, and the level of sperm was lower in SBMA than in SCA1 and DRPLA. Thus, spermatogenesis was suggested to be strongly associated with paternal anticipation. The mosaicism level was smaller in SBMA than in other (CAG), expanded disorders, and smallest in the SBMA carrier females. These findings demonstrate that the CAG repeat in SBMA is relatively stable in mitotic and meiotic processes, and there is a possibility that the lower mosaicism level of the carrier females compared with the SBMA patients is associated with X-linked recessive inheritance.
KW - Anticipation
KW - CAG repeat
KW - Cell mosaicism
KW - Dentatorubral and pallidoluysian atrophy
KW - Skeletal muscle
KW - Sperm
KW - Spinocerebellar ataxia type 1
KW - X-linked spinal and bulbar muscular atrophy
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U2 - 10.1111/j.1399-0004.1996.tb02367.x
DO - 10.1111/j.1399-0004.1996.tb02367.x
M3 - Article
C2 - 8946111
AN - SCOPUS:10344243027
SN - 0009-9163
VL - 50
SP - 133
EP - 137
JO - Clinical Genetics
JF - Clinical Genetics
IS - 3
ER -