2005 Fiscal Year Final Research Report Summary
Genetic epidemiology of hereditary hemorrhagic telangiectasia (HHT, Oslers disease)
| Project/Area Number |
16615001
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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 |
臨床疫学
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| Research Institution | Akita University |
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Principal Investigator |
SHIOYA Takanobu Akita University, School of Health Sciences, Dept of Phy Ther, Professor, 医学部, 教授 (90170852)
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| Co-Investigator(Kenkyū-buntansha) |
SATAKE Masahiro Akita University, School of Health Sciences, Dept of Phy Ther, Ass Professor, 医学部, 助教授 (10250903)
SASAKI Mahiro Akita University, School of Medicine, Dept of Pul Med, Associate Professor, 医学部, 助教授 (20221278)
KOIZUMI Akio Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (50124574)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Hereditary hemorrhagic telangiectasia / Genetic epidemiology / pulmonary arteriovenous malformation / cerebral artenovenous malformation / pulmonary rehabilitation / respiratory muscle training |
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| Research Abstract |
Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome) is an autosomal dominant disorder by aberrant vascular development, especially pulmonary arteriovenous malformation (AVM). We have investigated a genetic epidemiologic study in the Akita prefecture (population 1.2 million) located in northern Japan. Nine HHT patients patients who had been referred to tertiary-care hospitals were located and near the study county. A total of 137 pedigree members were traced of which 81 were alive and 32 were affected by HHT. Complicatiion associated with cerebral or pulmonary AVMs were proven in six out of seven families. Linkage analysis in two large families revealed a week yet suggestive linkage to the HHT1 locaus (encoding endoglin ; ENG). Three novel mutations were found in four families, all of which led to framesift ; a G to C transvertion at the splicing donor site of intron 3 (Inv3 + 1G>C) in one family, one base pair insertion (A) at nucleotide 828 (exon 7) of the endoglin cDNA in two large families (C.828-829 insA), and a four base pair deletion (AAAG) beginning with nucleotide 1120 (exon 8) of the endoglin cDNA (c.1120-1123 delAAAG) in one family. The insertion of A in exon 11 (c.1470-1471 insA) mutation found in one family has also been reported in a European family. No endoglin gene mutations were found in two families. The population prevalence of HHT in the county was estimated to 1:8,000-1:5,000, roughly comparable with those reported in European and U.S. populations, which is contradictory to the traditional view that HHT is rare among Asians. We recommend that families with HHT be screened for gene mutations in order that high-risk individuals receive early diagnosis and treatment initiation that will substantially alter their clinical course and prognosis.
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