title: Homozygous FIBP nonsense variant responsible of syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities.
abstract: The acidic fibroblast growth factor (FGF) intracellular binding protein (FIBP) interacts directly with the fibroblast growth factor FGF1. Although FIBP is known to be implicated in the FGF signaling pathway, its precise function remains unclear. Gain-of-function variants in several FGF receptors (FGFRs) are implicated in a wide spectrum of growth disorders from achondroplasia to overgrowth syndromes. In a unique case from a consanguineous union presenting with overgrowth, macrocephaly, retinal coloboma, large thumbs, severe varicose veins and learning disabilities, exome sequencing identified a homozygous nonsense FIBP variant. The patient's fibroblasts exhibit FIBP cDNA degradation and an increased proliferation capacity compared with controls. The phenotype defines a new multiple congenital abnormalities (MCA) syndrome, overlapping with the heterogeneous group of overgrowth syndromes with macrocephaly. The different clinical features can be explained by the alteration of the FGFR pathway. Taken together, these results suggest the implication of FIBP in a new autosomal recessive MCA.
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.|Centre de Référence Maladies Rares, Anomalies du Développement et Syndrome Malformatifs de l'Est et Centre de Génétique, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Duplomb-Jego
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: F
authors.initials: F
authors.lastname: Limoge
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: D
authors.initials: D
authors.lastname: Picot
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Centre de Référence Maladies Rares, Anomalies du Développement et Syndrome Malformatifs de l'Est et Centre de Génétique, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: A
authors.initials: A
authors.lastname: Masurel
authors.affiliation: Service d'Angiologie, CHU Bocage, Dijon, France.
authors.forename: B
authors.initials: B
authors.lastname: Terriat
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Champilou
authors.affiliation: Centre de Référence Maladies Rares, Anomalies du Développement et Syndrome Malformatifs de l'Est et Centre de Génétique, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: D
authors.initials: D
authors.lastname: Minot
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.|Laboratoire de Génétique Moléculaire, PTB, CHU, Dijon, France.
authors.forename: J
authors.initials: J
authors.lastname: St-Onge
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Kuentz
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Duffourd
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.|Centre de Référence Maladies Rares, Anomalies du Développement et Syndrome Malformatifs de l'Est et Centre de Génétique, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-9271-3961
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.|Laboratoire de Génétique Moléculaire, PTB, CHU, Dijon, France.
authors.forename: J-B
authors.initials: JB
authors.lastname: Rivière
authors.affiliation: FHU-TRANSLAD, CHU Dijon, France.|Equipe EA4271 GAD, Université de Bourgogne, Dijon, France.|Centre de Référence Maladies Rares, Anomalies du Développement et Syndrome Malformatifs de l'Est et Centre de Génétique, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D003241:Consanguinity; D059472:Exome / Q000235:genetics; D005124:Eye Abnormalities; D005260:Female; D014644:Genetic Variation; D006130:Growth Disorders; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006720:Homozygote; D006801:Humans; D007859:Learning Disabilities; D008297:Male; D058627:Megalencephaly; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; C116274:FIBP protein, human; D008565:Membrane Proteins
keywords: FGF1; FIBP; macrocephaly; overgrowth; retinal coloboma