2019 Fiscal Year Final Research Report

Identification for susceptibility genes of mandibular pragmatism from the results of next-generation sequencing

Research Project

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Project/Area Number	17K11949
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Orthodontics/Pediatric dentistry
Research Institution	Fukuoka Dental College
Principal Investigator	KAJII Takashi 福岡歯科大学, 口腔歯学部, 准教授 (60322822)
Co-Investigator(Kenkyū-buntansha)	岡晃東海大学, 総合医学研究所, 講師 (80384866) 八田光世福岡歯科大学, 口腔歯学部, 教授 (30344518)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	歯科矯正学 / 基礎ゲノム科学
Outline of Final Research Achievements	To explore variants related to mandibular prognathism, we undertook whole-exome sequencing in a Japanese pedigree. The pedigree was ascertained as mandibular prognathism. Four affected individuals across 2 generations and 5 unaffected individuals were chosen for whole-exome sequencing. Five non-synonymous single-nucleotide variants (SNVs) were detected in all 4 affected individuals, but in none of the 5 unaffected individuals. A non-synonymous SNV of the BEST3 gene, Chr12(GRCh37):g.70048878G > T, NM_032735.2:c.1816C > A, p.(L606I), was identified as rare missense variant. BEST3 is located on chromosome 12q15 and encodes bestrophin 3 from the bestrophin family of anion channels. The 4 other non-synonymous SNVs of UBASH3B, OR6M1, OR8D4, and OR8B4 were not considered plausible candidates for mandibular prognathism. Our whole-exome sequencing implicates a rare non-synonymous SNV of BEST3 as a candidate for mandibular prognathism in the Japanese pedigree.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	骨格性下顎前突症の感受性候補遺伝子の１つがBEST3遺伝子であれば、成長期の骨格性下顎前突症患者の試料からこの遺伝子の一塩基変異をPCRにて確認することにより、その患者に下顎骨の爆発的な過成長が成長終了期に認められるかどうかを成長期のうちに判断することが可能になる。言い換えれば、矯正歯科治療の一つである成長のコントロールを成長期に行っても、成長終了期には顎矯正手術が必要となってしまうことを成長期のうちに判断することが可能となる。これは矯正歯科治療において革新的なことであり、不必要な成長のコントロール治療を回避することが可能となり、国民の健康増進に寄与するものである。