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.
Authors
- Juliane Isaac (ORCID: https://orcid.org/0000-0001-7898-022X)
- Muriel de La Dure‐Molla (ORCID: https://orcid.org/0000-0003-3557-2845)
- Shélida Vasconcelos Braz (ORCID: https://orcid.org/0000-0003-1484-109X)
- Heliana Dantas Mestrinho (ORCID: https://orcid.org/0000-0002-8345-642X)
- Nunthawan Nowwarote (ORCID: https://orcid.org/0000-0001-5315-5565)
- Ana Carolina Acevedo (ORCID: https://orcid.org/0000-0001-7110-7110)
- André Ferreira Leite (ORCID: https://orcid.org/0000-0002-7803-4740)
- Neysa Aparecida Tinoco Regattieri
- Luiz Cláudio Castro (ORCID: https://orcid.org/0000-0002-9166-1837)
- Juliana F. Mazzeu (ORCID: https://orcid.org/0000-0002-6161-0510)
- Caroline Lourenço de Lima (ORCID: https://orcid.org/0000-0002-2495-6416)
- Daniel R. Carvalho (ORCID: https://orcid.org/0000-0002-3410-9704)
- Benjamin Fournier (ORCID: https://orcid.org/0000-0003-4383-7524)
- Guilherme Santos (ORCID: https://orcid.org/0000-0003-1489-2161)
- Paulo Tadeu de Souza Figueiredo (ORCID: https://orcid.org/0000-0002-7285-7869)
- Paulo Márcio Yamaguti (ORCID: https://orcid.org/0000-0002-9366-3852)
- Ariane Berdal (ORCID: https://orcid.org/0000-0001-5833-5813)
- Audrey Asselin
- Nathalia de Aguiar Montenegro
Institutions
- Universidade de Brasília (BR)
- Inserm (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Hôpital Rothschild (FR)
- Sorbonne Paris Cité (FR)
- Sarah Network of Rehabilitation Hospitals (BR)
- Hospital Universitário de Brasília (BR)
- University Center of Brasília (BR)
- Universidade Federal do Amazonas (BR)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1111/cge.14779
- Primary Topic
- Dermatological and Skeletal Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior