title: Two cases with de novo 3q26.31 microdeletion suggest a role for FNDC3B in human craniofacial development.
abstract: Here, we report strong evidence for a role of the FNDC3B gene in craniofacial development. Chromosomal microarray identified deletions at 3q26.31 in two patients with dysmorphic facial features. Parental FISH studies demonstrated that they are de novo; therefore, these two 3q26.31 microdeletions likely contribute to the patients' dysmorphic features. Interestingly, the minimal region of overlap contains only the FNDC3B gene. Ffibronectin domain III-containing protein 3B (FNDC3B), also known as factor for adipocyte differentiation-104 (FAD104), was first identified as a positive regulator of adipogenesis in a mouse model. Excitingly, further studies in a mouse model have recently demonstrated that FNDC3B is required for normal calvarial bone formation and negatively regulated calvarial cell differentiation through inhibition of BMP/Smad signaling. fndc3b-deficient mice have multiple cranial and skeletal malformations, such as craniosynostosis-like premature calvarial ossification, and skeletal deformities in the anterior fontanel and femurs. In summary, we report the first two patients with de novo 3q26.31 microdeletions. Both have dysmorphic features, consistent with the phenotypes seen in fndc3b-deficient mice in animal studies, which imply a critical role of FNDC3B in human craniofacial development. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Cytogenetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Cytogenetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Elyse B
authors.initials: EB
authors.lastname: Mitchell
authors.affiliation: Departments of Child Health and Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri.
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Gorski
authors.affiliation: Department of Child Health, University of Missouri School of Medicine, Columbia, Missouri.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Hollinger
authors.affiliation: Cytogenetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Hoppman
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D055028:Comparative Genomic Hybridization; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D038081:Organogenesis / Q000235:genetics*; D010641:Phenotype; D010808:Physical Examination
chemical_list: C543006:FNDC3B protein, human; D005353:Fibronectins
keywords: 3q26.31 microdeletion; FNDC3B; craniofacial development