| Background:Dentin dysplasia type I（DD-I）is a rare hereditary dentin developmental defect,characterized by short or absent tooth roots,abnormal loosening or even spontaneous loss,and pulp obliteration.Therefore,DD-I often leads to numerous tooth loosing when patients are young and causes occlusal disorders,which seriously affects the physical and mental health of patients.Hitherto,several pathogenic genes of DD-I have been found,including SMOC2,VPS4 B,and SSUH2,indicating that DD-I has the characteristic of genetic heterogeneity.However,the pathogenic mechanism of the known genes has not been fully elucidated,and whether there are other pathogenic genes are unclear.Objectives:Through the study of a DD-I family from northeast China,we aimed to understand the genetic patterns,clinical features and histopathological characteristics of DD-I and to screen the pathogenic genes.Methods:1.By inquiring the medical history,collecting the relevant information of family members,conducting clinical examination,imaging examination and laboratory examination,etc.,the pedigree map was drawn and the diagnosis of DD-I was made.2.HE staining and immunohistochemical staining were performed on the DD-I and normal tooth sections to observe tooth structures as well as Col I,Bone sialoprotein（BSP）and dentin sialoprotein（DSP）expression differences between DDI and control tooth.3.Screening the possible pathogenic genes through Next-Generation wholegenome Sequencing.Results:1.In the 5-generation family,except the family members who died and did not arrive at the scene,a total of 4 affected members were detected,distributed in two generations,and all of them were male patients;2.The proband had no systemic diseases,the bone development was basically normal,and the level of hormone ions in the body was normal;;3.The shape of the crown was basically normal.Panoramic radiograph revealed both deciduous and permanent teeth were all involved,the pulp cavity of the crown was often obliterated or crescent shaped,the root was short or absent,and the root tip was conical.In addition,some of the affected teeth had unexplained low density image.4.Compared with the normal teeth,the size,shape and color of the crown of the isolated diseased teeth were normal,but the length of the teeth was obviously shorter,with almost no root,and the ratio of crown to root was 3:1.The apical holes were not visible,and X-ray and CBCT suggested pulp obliteration.HE staining showed regular arrangement of dentin tubules in the crown of DD-I teeth,residual pulp,mass change of dentin in the inner layer,and almost no dentin tubules.Col-I immunohistochemical staining of affected teeth showed no significant difference from normal dentin.Immunohistochemical staining of BSP showed that the thickness of cementum was widened,the expression of BSP was weakly positive,and the boundary between BSP and dentin was not clear.DSP immunohistochemical staining showed that DSP expression was positive in normal cementum and peritubular dentin.The expression of DSP in DD-I dentin region was weakly positive and there was no normal dentin structure.5.SNV detection and statistical analysis revealed 4 missense mutations in DMP1.The product of the differential gene may be located in ECM,which may be related to focal adhesion pathway.Comparison analysis showed that the differential gene FAM20 C was related to tooth mineralization and was a candidate gene for disease.Conclusion:1.The genetic characteristics of this family are not clear and tend to be autosomal dominant inheritance.2.The clinical features are consistent with hereditary DD-I.3.Histological features suggest that the affected teeth in this family have both abnormal development of dentin and cementum.4.The results of whole genome sequencing indicate that the mutant gene in this family may be DMP1 or FAM20 C,which needs further verification. |
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