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For a
CAG count of 41, one person had onset at 25 years of age, another had onset
at 81 years of age. Keep this in mind while looking at the table below.
--Jerry
12Dec 2000
CAG
v Onset
CAG Repeat Sizing
The scatter plot is from A Physician's Guide to the Management
of Huntington's Disease 2nd ed.
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The Huntington's Disease (HD) gene was mapped to chromosome 4p16.3 in
1983 but eluded identification until 1993. When finally identified, the
gene ( IT15) was found to contain a CAG repeat within its 5'-end coding
sequence (Cell 72:971-983). This CAG repeat is expanded in individuals
with HD who may or may not be symptomatic. The presence of a CAG repeat
expansion is found in virtually all symptomatic HD individuals (N. Engl.
J. Med. 330:1401-1406).
Normal HD gene CAG repeats range from 10 - 29 repeats. A few normal individuals
(< 1%) have intermediate HD gene CAG repeats of 30 - 35 repeats.
Individuals affected with HD typically have at least one HD gene CAG
repeat of 36 repeats or greater. A recent review of > 1,100 affected
individuals showed that none had a CAG repeat of < 36 repeats. However,
it was also found that in a few rare instances (10 cases) individuals
having repeats of 36 - 39 repeats had remained asymptomatic by standard
clinical criteria at advanced age. In one exceptional case, a 95 year
old patient had 39 repeats (Rubinsztein et. al., 1996; Am. J. Hum. Genet.
59:16-22)
| CAG Repeat Size | Median Age at Onset(years) | * |
| 39 | 66 | (72-59) |
| 40 | 59 | (61-56) |
| 41 | 54 | (56-52) |
| 42 | 49 | (50-48) |
| 43 | 44 | (45-42) |
| 44 | 42 | (43-40) |
| 45 | 37 | (39-36) |
| 46 | 36 | (37-35) |
| 47 | 33 | (35-31) |
| 48 | 32 | (34-30) |
| 49 | 28 | (32-25) |
| 50 | 27 | (30-24) |
* (95% confidence interval)
Age by which 50% of individuals will be affected. |
Individuals who have an HD gene CAG repeat size close to the normal/affected boundary should be counseled in light of the sizes of the HD gene CAG repeat sizes found in any affected relatives and/or by considering clinical findings. There is a tendency to an earlier age-of-onset of HD symptoms with increasing CAG repeat number. A current review of 1,049 persons (the majority of whom were symptomatic) has provided a determination of the likelihood of an age-of-onset for a given CAG repeat size for repeats between 39 - 50 repeats (Brinkman et al., 1997; Am. J. Hum. Genet. 60:1202-1210). Summary data are reproduced in the table. For complete information, please refer to the cited article.
A Physician's Guide to the
Management of Huntington's Disease 2nd ed.
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