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. 1993 Dec;30(12):982–986. doi: 10.1136/jmg.30.12.982

Gametic but not somatic instability of CAG repeat length in Huntington's disease.

M E MacDonald 1, G Barnes 1, J Srinidhi 1, M P Duyao 1, C M Ambrose 1, R H Myers 1, J Gray 1, P M Conneally 1, A Young 1, J Penney 1, et al.
PMCID: PMC1016628  PMID: 8133508

Abstract

Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.

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Selected References

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