Kantaputra Piranit Nik, Dejkhamron Prapai, Intachai Worrachet, Ngamphiw Chumpol, Ketudat Cairns James R, Kawasaki Katsushige, Ohazama Atsushi, Olsen Bjorn, Tongsima Sissades, Angkurawaranon Salita
Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University.
Department of Pediatrics, Faculty of Medicine, Chiang Mai University.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Dec;132(6):e198-e207. doi: 10.1016/j.oooo.2021.01.023. Epub 2021 Jan 28.
Our objective was to investigate the molecular etiology of osteogenesis imperfecta type VIII and dental anomalies in 4 siblings of a Karen tribe family.
Four patients and their unaffected parents were studied by clinical and radiographic examination. In situ hybridization of P3h1 during early murine tooth development, whole-exome sequencing, and Sanger direct sequencing were performed.
A novel homozygous missense P3H1 mutation (NM_001243246.1; c.2141A>G; NP_001230175.1; p.Lys714Arg) was identified in all patients. Their unaffected parents were heterozygous for the mutation. The mutation is hypothesized to belong to isoform c of P3H1. Mutations in P3H1 are associated with autosomal recessive osteogenesis imperfecta type VIII. Hypodontia, a mesiodens, and single-rooted permanent second molars found in our patients have never been reported in patients with P3H1 mutations. Single-rooted second permanent molars or failure to form multiple roots implies effects of the P3H1 mutation on root development.
We report a novel P3H1 mutation as the underlying cause of osteogenesis imperfecta type VIII with dental anomalies. Our study suggests that isoform c of P3H1 is also a functional isoform of P3H1. We report, for the first time, to our knowledge, the association of P3H1 mutation and osteogenesis imperfecta type VIII with dental anomalies.
我们的目的是调查一个克伦族家庭中4名兄弟姐妹的VIII型成骨不全症和牙齿异常的分子病因。
通过临床和影像学检查对4名患者及其未受影响的父母进行研究。在小鼠牙齿早期发育过程中进行P3h1的原位杂交、全外显子测序和桑格直接测序。
在所有患者中均鉴定出一种新的纯合错义P3H1突变（NM_001243246.1；c.2141A>G；NP_001230175.1；p.Lys714Arg）。他们未受影响的父母为该突变的杂合子。该突变被推测属于P3H1的c亚型。P3H1突变与常染色体隐性VIII型成骨不全症相关。我们的患者中发现的缺牙、正中多生牙和单根恒牙第二磨牙在P3H1突变患者中从未有过报道。单根第二恒磨牙或未能形成多根意味着P3H1突变对牙根发育有影响。
我们报告了一种新的P3H1突变，它是伴有牙齿异常的VIII型成骨不全症的潜在病因。我们的研究表明，P3H1的c亚型也是P3H1的一种功能亚型。据我们所知，我们首次报告了P3H1突变和VIII型成骨不全症与牙齿异常的关联。
