A Novel Variant in Dentin Sialophosphoprotein (DSPP) Gene Causes Dentinogenesis Imperfecta Type III: Case Report.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2025-03-01 DOI:10.1002/mgg3.70087

Yan Wang, Ximin Xu, Yuzhe Ding, Guohua Yuan

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引用次数: 0

Abstract

Background: Hereditary dentin defects are a group of autosomal dominant disorders characterized by developmental abnormalities in dentin formation and mineralization. They can be categorized into dentin dysplasia and dentinogenesis imperfecta.

Methods: In this study, we report a Chinese family with dentinogenesis imperfecta type III (DGI-III). The proband, a 3-year-old girl, and her mother showed extremely rapid attrition and opalescent discoloration in their teeth. Besides, the primary teeth of the proband showed "shell teeth" radiographically, a phenotype characterized by abnormally enlarged pulp cavities and thin dentin, which are specific features of DGI-III. The clinical data was collected and the genomic DNA was extracted from their peripheral blood samples. Whole-exome sequencing and Sanger sequencing were performed to screen for variations. Then we preliminarily evaluated the secretion of the dentin sialophosphoprotein (DSPP) variant of this family and compared this variant with wild-type DSPP via western blot (WB) analysis in vitro.

Results: The results revealed a novel variant (NM_014208: exon2: c.38C>A: p.A13E) in the signal peptide coding region of the DSPP gene in both the proband and her mother, but not in her father, who had normal teeth. The secretion of the variant DSPP protein was not detected in Human embryonic kidney 293E cells via WB analysis.

Conclusion: Taken together, this study describes the clinical features and genetic etiology of a family with DGI-III, expanding the range of variants that cause DGI-III and enriching the phenotypes associated with variants in the signal peptide segment of DSPP. Functional analysis reveals that this variant disrupts DSPP protein secretion.

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牙本质唾液磷酸蛋白（DSPP）基因的新变异导致牙本质发育不全III型：病例报告。

背景：遗传性牙本质缺陷是一组常染色体显性遗传病，其特征是牙本质形成和矿化发育异常。可分为牙本质发育不全和牙本质发育不全。方法：在本研究中，我们报告了一个患有牙本质发育不全III型（DGI-III）的中国家庭。先证者是一名3岁的女孩，她和她的母亲的牙齿出现了非常迅速的磨损和乳白色变色。先证者的乳牙x线表现为“壳牙”，表现为牙髓腔异常增大，牙本质薄，这是DGI-III的特异性特征。收集临床数据，并从外周血样本中提取基因组DNA。进行全外显子组测序和Sanger测序以筛选变异。然后，我们初步评估了该家族牙本质唾液磷蛋白（DSPP）变体的分泌情况，并通过体外western blot （WB）分析将该变体与野生型DSPP进行了比较。结果：先证者及其母亲在DSPP基因信号肽编码区均发现了一个新的变异（NM_014208：外显子2:c.38C> a: p.A13E），而在其正常牙齿的父亲中未发现。WB分析显示，人胚胎肾293E细胞中未检测到DSPP蛋白的分泌。结论：综上所述，本研究描述了一个DGI-III家族的临床特征和遗传病因，扩大了导致DGI-III的变异范围，丰富了与DSPP信号肽段变异相关的表型。功能分析显示该变异破坏DSPP蛋白分泌。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.