2000 Fiscal Year Final Research Report Summary
Study on genetic diagnosis for glycogen storage disease type III and relationship between enzymatic activities and clinical manifestations
| Project/Area Number |
11670807
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Okinaka Memorial Institute for Medical Research |
|---|
Principal Investigator |
OKUBO Minoru Okinaka Memorial Institute for Medical Research, Research Fellow, 研究員 (60241238)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Keywords | Glycogen storage disease type III / Glycogen debranching enzyme / Mutation / Glycogen-binding domain / AGL |
|---|
| 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.
|
