Laboratory of Oral Histopathology, Health Sciences Faculty and Oral Care Center for Inherited Diseases, University of Brasilia, Brasília, Brazil.
School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Arch Oral Biol. 2021 Sep;129:105206. doi: 10.1016/j.archoralbio.2021.105206. Epub 2021 Jul 1.
To perform a phenotypic characterization of the dento-osseous anomalies in a Brazilian family with Familial Adenomatous Polyposis (FAP) and to investigate the adenomatous polyposis coli (APC) causative variant.
The study included a family of 14 individuals (Group A: affected; Group B: non-affected). The frequency of radiographic findings in both groups was evaluated according to the Dental Panoramic Radiograph Score (DPRS) diagnostic method. The accuracy and reproducibility of DPRS were tested. The DNA was isolated from the index patient's saliva and submitted to whole-exome and Sanger sequencing approach.
DPRS ≥ 7 was observed in 80 % of Group A but in none of Group B. The most common findings in Group A were dense bone islands (60 %), hazy sclerosis (40 %), osteomas (40 %), and supernumerary tooth (20 %). DPRS has proved to be a reliable method while DPRS ≥ 5 and DPRS ≥ 7 were taken as positive for FAP, and reproducible diagnosis test considering that the evaluators correctly identified the affected patients (Kappa agreement>0.8, p = 0.002). A nonsense heterozygous mutation in the APC gene (c.1370C > G; p.Ser457*) of the index case was detected.
FAP patients have a higher frequency of dento-osseous anomalies (p = 0.005). Bone abnormalities were more prevalent than dental anomalies (p = 0.001). Thus, FAP patients should be referred for dental examination and genetic counseling to perform early diagnosis of dento-osseous anomalies and evaluate the implications of the molecular findings in each particular family.
对一个具有家族性腺瘤性息肉病(FAP)的巴西家庭的牙-骨异常进行表型特征分析,并研究腺瘤性结肠息肉病基因(APC)的致病变体。
该研究纳入了一个 14 人的家庭(A 组:受影响的;B 组:未受影响的)。根据口腔全景放射评分(DPRS)诊断方法,评估两组的放射学发现频率。测试了 DPRS 的准确性和可重复性。从索引患者的唾液中提取 DNA,并进行全外显子组和 Sanger 测序分析。
A 组中 80%的患者 DPRS≥7,但 B 组中无一例患者 DPRS≥7。A 组最常见的发现是密质骨岛(60%)、模糊性硬化(40%)、骨瘤(40%)和额外牙(20%)。DPRS 是一种可靠的方法,当 DPRS≥5 和 DPRS≥7 被视为 FAP 的阳性结果时,考虑到评估者正确地识别了受影响的患者,DPRS 是一种可重复的诊断测试(Kappa 一致性>0.8,p=0.002)。在索引病例中检测到 APC 基因(c.1370C>G;p.Ser457*)的无义杂合突变。
FAP 患者牙-骨异常的频率更高(p=0.005)。骨异常比牙齿异常更常见(p=0.001)。因此,FAP 患者应转介进行口腔检查和遗传咨询,以便对牙-骨异常进行早期诊断,并评估每个特定家庭中分子发现的影响。