Heterozygous FGFR1 mutation may be responsible for an incomplete form of osteoglophonic dysplasia, characterized only by radiolucent bone lesions and teeth retentions

Pauline Marzin; Geneviève Baujat; Déborah Gensburger; Céline Huber; Christine Bole; Michel Panuel; Georges Finidori; Muriel De la Dure; Valérie Cormier-Daire

doi:10.1016/j.ejmg.2019.103729

Heterozygous FGFR1 mutation may be responsible for an incomplete form of osteoglophonic dysplasia, characterized only by radiolucent bone lesions and teeth retentions

Eur J Med Genet. 2020 Feb;63(2):103729. doi: 10.1016/j.ejmg.2019.103729. Epub 2019 Jul 15.

Authors

Pauline Marzin¹, Geneviève Baujat¹, Déborah Gensburger², Céline Huber¹, Christine Bole³, Michel Panuel⁴, Georges Finidori⁵, Muriel De la Dure⁶, Valérie Cormier-Daire⁷

Affiliations

¹ Department of Medical Genetics, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, IMAGINE Institute, Necker Enfants Malades Hospital, Paris, France.
² Department of Rheumatology, Edouard Herriot Hospital, Lyon, France.
³ Genomic Core Facility, INSERM UMR1163, Imagine Institute, Paris, France.
⁴ Aix Marseille University, CNRS, EFS, ADES, Marseille, France.
⁵ Department of Pediatric Orthopedics, Université Paris Descartes, Sorbonne Paris Cité, Hôpital Necker Enfants Malades, Paris, France.
⁶ Department of Medical Genetics, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, IMAGINE Institute, Necker Enfants Malades Hospital, Paris, France; Laboratory of Molecular Oral Pathophysiology, Centre de Recherche des Cordeliers, INSERM UMRS 1138, University Paris-Descartes, University Pierre et Marie Curie-Paris, 75006, Paris, France.
⁷ Department of Medical Genetics, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, IMAGINE Institute, Necker Enfants Malades Hospital, Paris, France. Electronic address: valerie.cormier-daire@inserm.fr.

PMID: 31319224
DOI: 10.1016/j.ejmg.2019.103729

Abstract

Non-ossifying fibromas are seen in different disorders recognizable by specific features. Indeed, osteoglophonic dysplasia (OD) is characterized by radiolucent bone lesions associated with severe short stature, dysmorphism and failure of dental eruption. This syndrome is caused by heterozygous activating mutations in the immunoglobulin-like D3 domain of the FGFR1 gene, encoding a tyrosine kinase. Here, we report three patients from the same family presenting with radiolucent bone lesions and teeth retentions. Exome sequencing allowed identification of a novel mutation c.917C > T, p. Pro306Leu in exon 7 of the FGFR1 gene. Our patients present with normal stature and no severe dysmorphism. This report describes a mild form of OD and expands the phenotype related to FGFR1 mutations. These findings emphasize the need to consider FGFR1 variants in the case of multiple non-ossifying bone lesions associated with dental eruption anomalies.

Keywords: FGFR1; Failure of tooth eruption; Non-ossifying fibromas; Osteoglophonic dysplasia.

Publication types

Case Reports

MeSH terms

Child
Exome Sequencing
Exons / genetics
Female
Heterozygote
Humans
Middle Aged
Mutation
Osteochondrodysplasias / diagnosis
Osteochondrodysplasias / diagnostic imaging
Osteochondrodysplasias / enzymology
Osteochondrodysplasias / genetics*
Pedigree
Phenotype
Protein Domains / genetics
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism
Receptor, Fibroblast Growth Factor, Type 1 / genetics*
Tooth Abnormalities / diagnosis
Tooth Abnormalities / diagnostic imaging
Tooth Abnormalities / genetics*

Substances

FGFR1 protein, human
Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1

Supplementary concepts

Osteoglophonic dwarfism