Two cases with de novo 3q26.31 microdeletion suggest a role for FNDC3B in human craniofacial development

Yang Cao, Elyse B. Mitchell, Jerome L. Gorski, Cassandra Hollinger, Nicole L. Hoppman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)3276-3281
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number12
StatePublished - Dec 1 2016


  • 3q26.31 microdeletion
  • FNDC3B
  • craniofacial development


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