Bigoni Stefania, Neri Marcella, Scotton Chiara, Farina Roberto, Sabatelli Patrizia, Jiang Chongyi, Zhang Jianguo, Falzarano Maria Sofia, Rossi Rachele, Ognibene Davide, Selvatici Rita, Gualandi Francesca, Bosshardt Dieter, Perri Paolo, Campa Claudio, Brancati Francesco, Salvatore Marco, De Stefano Maria Chiara, Taruscio Domenica, Trombelli Leonardo, Fang Mingyan, Ferlini Alessandra
Medical Genetics Unit, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Research Centre for the Study of Periodontal and Peri-Implant Diseases, University of Ferrara, Ferrara, Italy.
Front Genet. 2019 Jan 21;9:723. doi: 10.3389/fgene.2018.00723. eCollection 2018.
Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the gene. Dominant splicing mutations in are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of mutations.
已知只有少数参与牙齿发育和形态形成的基因会导致孟德尔遗传疾病中的牙齿异常。我们研究了一个来自巴基斯坦的近亲繁殖家族，家族中两个表亲出生的兄弟患有早期牙齿脱落，并伴有特殊的牙齿异常，其特征是牙骨质形成缺失。全外显子组测序在该基因中发现了一个H2665L纯合序列变异。已知该基因的显性剪接突变会导致瓦格纳综合征或玻璃体视网膜病变。我们研究了这两名患者的牙齿形态，同时通过蛋白质免疫印迹分析评估了多功能蛋白聚糖的表达。在哥哥身上发现了玻璃体视网膜病变的早期迹象，而其父母完全正常。我们的研究结果表明，纯合隐性H2665L错义序列变异通过牙骨质合成缺失损害了牙根的正常形态，并且还与早发性隐性瓦格纳综合征相关，从而扩展了该基因突变的表型突变情况和遗传模式。
