Paulo Marcio Yamaguti, Shélida Vasconcelos Braz, Audrey Asselin, André Ferreira Leite, Caroline Lourenço de Lima, Daniel Rocha de Carvalho, Heliana Dantas Mestrinho, Paulo Tadeu Figueiredo, Guilherme Santos, Nathalia de Aguiar Montenegro, Nunthawan Nowwarote, Benjamin Philippe Jacques Fournier, Muriel de La Dure-Molla, Ariane Berdal, Luiz Claudio Gonçalves de Castro, Neysa Aparecida Tinoco Regattieri, Juliana Forte Mazzeu, Juliane Isaac, Ana Carolina Acevedo
{"title":"一种新型的骨骼发育不良伴上颌骨增生、牙龈增生和牙充血。","authors":"Paulo Marcio Yamaguti, Shélida Vasconcelos Braz, Audrey Asselin, André Ferreira Leite, Caroline Lourenço de Lima, Daniel Rocha de Carvalho, Heliana Dantas Mestrinho, Paulo Tadeu Figueiredo, Guilherme Santos, Nathalia de Aguiar Montenegro, Nunthawan Nowwarote, Benjamin Philippe Jacques Fournier, Muriel de La Dure-Molla, Ariane Berdal, Luiz Claudio Gonçalves de Castro, Neysa Aparecida Tinoco Regattieri, Juliana Forte Mazzeu, Juliane Isaac, Ana Carolina Acevedo","doi":"10.1111/cge.14779","DOIUrl":null,"url":null,"abstract":"<p><p>This study reports a skeletal disorder marked by facial dysmorphism and a distinct oro-dental phenotype including premaxillary and gingival overgrowth and hypercementosis. Whole-exome sequencing identified a homozygous missense variant in ENPP5 (c.173G>T; p.Gly58Val), affecting a conserved glycine residue predicted to be within a putative active binding site of the ENPP5 protein. In mice, RNA-seq and immunofluorescence confirmed Enpp5 expression in functional osteoblasts of the maxilla and mandible, periodontal ligament, odontoblasts, and ameloblasts. RT-qPCR confirmed region-specific expression, with higher Enpp5 expression in premaxillary-maxillary bones compared to the tibia, suggesting site-dependent functional roles. This report links, for the first time, a biallelic ENPP5 variant to a novel syndrome involving premaxillary development, bone and cementum growth, highlighting the need for further functional and clinical investigation.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Novel Skeletal Dysplasia With Premaxilla Overgrowth, Gingival Hyperplasia, and Dental Hypercementosis.\",\"authors\":\"Paulo Marcio Yamaguti, Shélida Vasconcelos Braz, Audrey Asselin, André Ferreira Leite, Caroline Lourenço de Lima, Daniel Rocha de Carvalho, Heliana Dantas Mestrinho, Paulo Tadeu Figueiredo, Guilherme Santos, Nathalia de Aguiar Montenegro, Nunthawan Nowwarote, Benjamin Philippe Jacques Fournier, Muriel de La Dure-Molla, Ariane Berdal, Luiz Claudio Gonçalves de Castro, Neysa Aparecida Tinoco Regattieri, Juliana Forte Mazzeu, Juliane Isaac, Ana Carolina Acevedo\",\"doi\":\"10.1111/cge.14779\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study reports a skeletal disorder marked by facial dysmorphism and a distinct oro-dental phenotype including premaxillary and gingival overgrowth and hypercementosis. Whole-exome sequencing identified a homozygous missense variant in ENPP5 (c.173G>T; p.Gly58Val), affecting a conserved glycine residue predicted to be within a putative active binding site of the ENPP5 protein. In mice, RNA-seq and immunofluorescence confirmed Enpp5 expression in functional osteoblasts of the maxilla and mandible, periodontal ligament, odontoblasts, and ameloblasts. RT-qPCR confirmed region-specific expression, with higher Enpp5 expression in premaxillary-maxillary bones compared to the tibia, suggesting site-dependent functional roles. This report links, for the first time, a biallelic ENPP5 variant to a novel syndrome involving premaxillary development, bone and cementum growth, highlighting the need for further functional and clinical investigation.</p>\",\"PeriodicalId\":10354,\"journal\":{\"name\":\"Clinical Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cge.14779\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.14779","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
A Novel Skeletal Dysplasia With Premaxilla Overgrowth, Gingival Hyperplasia, and Dental Hypercementosis.
This study reports a skeletal disorder marked by facial dysmorphism and a distinct oro-dental phenotype including premaxillary and gingival overgrowth and hypercementosis. Whole-exome sequencing identified a homozygous missense variant in ENPP5 (c.173G>T; p.Gly58Val), affecting a conserved glycine residue predicted to be within a putative active binding site of the ENPP5 protein. In mice, RNA-seq and immunofluorescence confirmed Enpp5 expression in functional osteoblasts of the maxilla and mandible, periodontal ligament, odontoblasts, and ameloblasts. RT-qPCR confirmed region-specific expression, with higher Enpp5 expression in premaxillary-maxillary bones compared to the tibia, suggesting site-dependent functional roles. This report links, for the first time, a biallelic ENPP5 variant to a novel syndrome involving premaxillary development, bone and cementum growth, highlighting the need for further functional and clinical investigation.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease