FAM111A mutations result in hypoparathyroidism and impaired skeletal development

Sheila Unger, Maria W. Górna, Antony Le Béchec, Sonia Do Vale-Pereira, Maria Francesca Bedeschi, Stefan Geiberger, Giedre Grigelioniene, Eva Horemuzova, Faustina Lalatta, Ekkehart Lausch, Cinzia Magnani, Sheela Nampoothiri, Gen Nishimura, Duccio Petrella, Francisca Rojas-Ringeling, Akari Utsunomiya, Bernhard Zabel, Sylvain Pradervand, Keith Harshman, Belinda Campos-XavierLuisa Bonafé, Giulio Superti-Furga, Brian Stevenson, Andrea Superti-Furga

Research output: Contribution to journalArticlepeer-review


Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.

Original languageEnglish
Pages (from-to)990-995
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - Jun 6 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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