| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen-debranching enzyme (AGL). Recent studies of the AGL gene have revealed the prevalent mutations in North African Jewish and Caucasian populations, but whether these common mutations are present in other ethnic groups remains unclear. We have investigated 10 Japanese GSD III patients from 9 families and identified 10 mutations, including one splicing mutation (IVS14+1G>T) previously reported by us, together with 9 novel ones : 1 nonsense mutation (L124X), 3 deletions (587delC, 2399delC, and 4216-4217delAG), 1 insertion (2072-2073insA), 2 splice site mutations
(IVS29-IG>C, IVS33+5G>A), 1 missense mutation (G1448R), and 1 duplication (4735-4736insTAT). The missense mutation and duplication presumably alter the tertiary structure of a putative glycogen-binding site located at the carboxyl terminal, and the rest are predicted to cause synthesis of truncated proteins lacking the glycogen-binding site. These results show the importance of the integrity of the carboxy terminal domain in the AGL protein and the molecular heterogeneity of GSD III in Japan.
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