2021 Fiscal Year Final Research Report
Hereditary folate malabsorption with a novel mutation in SLC46A1
| Project/Area Number |
16K20871
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Orthodontics/Pediatric dentistry
Pediatrics
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-04-01 – 2022-03-31
|
| Keywords | PCFT / SLC46A1 / deep intronic mutation / HFM |
|---|
| Outline of Final Research Achievements |
Hereditary folate malabsorption (HFM) is an autosomal recessive disease caused by mutations in SLC46A1 encoding the proton-coupled folate transporter (PCFT), a type of primary immunodeficiency. There are few cases in the past in which treatment has been successful without sequelae. We advanced functional analysis of the newly reported gene mutation and aimed to establish effective treatment standards for HFM.
During the study period, it was confirmed that folate malabsorption in the patient was due to a combination of genetic mutations from parents. And, EBV-LCL (human immortalized B cell line) derived from the patient was established, and the effect on the hematocyocyte system was examined. In addition, PCFT expression analysis of HeLa cells (human cervical cancer-derived cell lines) and folate transportant ability of mutant PCFT were analyzed.
|
| Free Research Field |
小児・障害者歯科
|
| Academic Significance and Societal Importance of the Research Achievements |
申請者らが報告した遺伝子変異については日本人特有の創始者変異あるいは世界共通でみられるホットスポットの可能性がある。国内外のゲノムデータベース検索でも該当はないが、今後情報が集積されるにつれて明らかになる可能性がある。また今後の新規HFM患者の遺伝子解析においては、当該変異をピンポイントで検索することでより早期の診断治療につながり得ると考えられる。葉酸取り込み能の解析はより安全かつ簡便に施行できるため、機能解析の一助となる。
本研究は、原因不明の原発性免疫不全症とされ早期に適切な治療に到達しない潜在的患者に対し、その早期診断および治療に寄与するものである。
|
