1999 Fiscal Year Final Research Report Summary
Analysis of ankyrin gene mutations in hereditary spherocytosis
| Project/Area Number |
09672369
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
IDEGUCHI Hirosho Fukuoka University. School of Medicine. Assistant professor, 医学部, 助教授 (30131808)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Hereditary spherocytosis / Ankyrin / Gene analysis |
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| Research Abstract |
We analyzed all exons (exon 1 - exon 42) and promotor region of ankyrin gene in 36 Japanese patients with hereditary spherocytosis (HS). Genomic DNAs were extracted from peripheral blood leukocytes and PCR (polymerase chain reaction)-amplified DNA fragments were subjected to screen ankyrin mutations by non-RI SSCP (single strand conformation polymorphism) method. The DNA fragments showing abnormal SSCPs were analyzed by direct DNA sequencing. As the results, we found 19 ankyrin gene mutations : 2 nonsense mutations, 6 missense mutations, 1 deletional mutation (deletion of 8 bases in intron), 1 intronic base substitution, and 9 silent mutations. Two nonsense mutations (E886X : GAG - TAG ; K1140X : AAG - TAG) were novel mutations that have not been reported, and may be directly involved in ankyrin deficiency which result in reduced assembly of underlying cytoskeletal proteins. Although further investigation should be needed to clarify whether 6 missense mutations are the primary defects of HS or mere polymorphisms, it was a notable evidence that 3 patients were a homozygote of the missense mutation (I1075T : ATC - ACC). We showed ankyrin gene mutations are one of the cause of Japanese patients with HS and these incidence may be 10 - 20%.
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