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FAM111A mutations result in hypoparathyroidism and impaired skeletal development.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2013 Jun 06; Vol. 92 (6), pp. 990-5. Date of Electronic Publication: 2013 May 16. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Abnormalities, Multiple diagnostic imaging
Abnormalities, Multiple mortality
Abnormalities, Multiple pathology
Adolescent
Adult
Bone Diseases, Developmental mortality
Bone Diseases, Developmental pathology
Child
Craniofacial Abnormalities mortality
Craniofacial Abnormalities pathology
Dwarfism diagnostic imaging
Dwarfism mortality
Genetic Association Studies
Heterozygote
Humans
Hyperostosis, Cortical, Congenital diagnostic imaging
Hyperostosis, Cortical, Congenital mortality
Hypocalcemia diagnostic imaging
Hypocalcemia mortality
Hypoparathyroidism diagnostic imaging
Hypoparathyroidism mortality
Infant
Infant, Newborn
Male
Mutation, Missense
Parathyroid Hormone deficiency
Radiography
Abnormalities, Multiple genetics
Bone Diseases, Developmental genetics
Craniofacial Abnormalities genetics
Dwarfism genetics
Hyperostosis, Cortical, Congenital genetics
Hypocalcemia genetics
Hypoparathyroidism genetics
Receptors, Virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 92
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 23684011
- Full Text :
- https://doi.org/10.1016/j.ajhg.2013.04.020