Periodontal disease and FAM20A mutations
Periodontal disease and FAM20A mutations
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DOI：
10.1038/jhg.2017.26
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发表时间：
2017-07-01
影响因子：
3.5
通讯作者：
Chaisrisookumporn, Nipon
中科院分区：
文献类型：
--
作者：
Kantaputra, Piranit Nik;Bongkochwilawan, Chotika;Chaisrisookumporn, Nipon
牙釉质-肾-牙龈综合征（Enamel-renal-gingival syndrome，ERGS; OMIM #204690）是一种罕见的由FAM 20 A基因突变引起的常染色体隐性遗传疾病，以肾钙质沉着症、肾石症、牙釉质发育不全、发育不全型、牙龈纤维瘤病和其他牙齿异常（包括牙发育不全和未萌出的牙）为特征。我们报告三名患者和他们的家庭的结果提示ERGS。对所有患者及其家族成员进行FAM 20 A基因突变分析。FAM 20 A纯合移码突变和复合杂合突变的患者具有典型的临床表现沿着牙周炎。另一个在外显子10有一个新的纯合错义突变，轻度牙龈纤维瘤病和肾脏钙化。牙周炎在我们的患者可能是一个综合征的组成部分，在以前的报告中类似的结果表明更多的巧合。Fam 20 a是增加Fam 20 c激酶活性的变构激活剂。我们推测，在我们的FAM 20 A突变患者中，FAM 20 A激活FAM 20 C的缺乏可能导致牙釉质形成障碍、异常骨重建和牙周炎。肾钙质沉着症似乎不是一个一致的发现综合征和错义突变可能与轻度牙龈纤维瘤病。在这里，我们报告了3例FAM 20 A纯合或复合杂合突变的患者，并发现扩展了这种疾病的表型谱，表明蛋白质截短与更大的临床严重程度相关。
Enamel-renal-gingival syndrome (ERGS; OMIM #204690), a rare autosomal recessive disorder caused by mutations in FAM20A, is characterized by nephrocalcinosis, nephrolithiasis, amelogenesis imperfecta, hypoplastic type, gingival fibromatosis and other dental abnormalities, including hypodontia and unerupted teeth with large dental follicles. We report three patients and their families with findings suggestive of ERGS. Mutation analysis of FAM20A was performed in all patients and their family members. Patients with homozygous frameshift and compound heterozygous mutations in FAM20A had typical clinical findings along with periodontitis. The other had a novel homozygous missense mutation in exon 10, mild gingival fibromatosis and renal calcifications. The periodontitis in our patients may be a syndrome component, and similar findings in previous reports suggest more than coincidence. Fam20a is an allosteric activator that increases Fam20c kinase activity. It is hypothesized that lack of FAM20A activation of FAM20C in our patients with FAM20A mutations might have caused amelogenesis imperfecta, abnormal bone remodeling and periodontitis. Nephrocalcinosis appears not to be a consistent finding of the syndrome and the missense mutation may correlate with mild gingival fibromatosis. Here we report three patients with homozygous or compound heterozygous mutations in FAM20A and findings that extend the phenotypic spectrum of this disorder, showing that protein truncation is associated with greater clinical severity.