Reference : FAM111A mutations result in hypoparathyroidism and impaired skeletal development
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/27300
FAM111A mutations result in hypoparathyroidism and impaired skeletal development
English
Unger, Sheila [Department of Pediatrics, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland, Medical Genetics Service, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland]
Górna, Maria W. [CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, 1090 Vienna, Austria]
Le Béchec, Antony [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Do Vale-Pereira, Sonia [Department of Pediatrics, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland]
Bedeschi, Maria Francesca [Clinical Genetic Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20100 Milano, Italy]
Geiberger, Stefan [Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden]
Grigelioniene, Giedre [Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden]
Horemuzova, Eva [Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden]
Lalatta, Faustina [Clinical Genetic Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20100 Milano, Italy]
Lausch, Ekkehart [Paediatric Genetics Division, Centre for Paediatrics and Adolescent Medicine, Freiburg University Hospital, 79106 Freiburg, Germany]
Magnani, Cinzia [Department of Neonatal Intensive Care Unit, University of Parma, 43126 Parma, Italy]
Nampoothiri, Sheela [Amrita Institute of Medical Sciences and Research Center, Department of Pediatric Genetics, AIMS Ponekkara, Cochin, Kerala 682 041, India]
Nishimura, Gen [Department of Radiology and Medical Imaging, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose 204-0021, Japan]
Petrella, Duccio [Department of Pathology, Niguarda Cà Granda Hospital, 20162 Milano, Italy]
Rojas-Ringeling, Francisca [Genética Clínica, Hospital Clínico Universidad de Chile, Santiago 8380000, Chile]
Utsunomiya, Akari [Department of Pediatrics, Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8553, Japan]
Zabel, Bernhard [Paediatric Genetics Division, Centre for Paediatrics and Adolescent Medicine, Freiburg University Hospital, 79106 Freiburg, Germany]
Pradervand, Sylvain [Genomic Technologies Facility, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland]
Harshman, Keith [Genomic Technologies Facility, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland]
Campos-Xavier, Belinda [Department of Pediatrics, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland]
Bonafé, Luisa [Department of Pediatrics, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland]
Superti-Furga, Giulio [CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, 1090 Vienna, Austria]
Stevenson, Brian [Vital-IT High Performance Computing Center, Swiss Institute of Bioinformatics, University of Lausanne, 1015 Lausanne, Switzerland]
Superti-Furga, Andrea [Department of Pediatrics, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland]
2013
American Journal of Human Genetics
92
6
990-995
Yes (verified by ORBilu)
International
0002-9297
[en] FAM 111 A protein ; Abnormalities, Multiple ; Adolescent ; Adult ; Bone Diseases, Developmental ; Child ; Craniofacial Abnormalities ; Dwarfism ; Genetic Association Studies ; Heterozygote ; Humans ; Hyperostosis, Cortical, Congenital ; Hypocalcemia ; Hypoparathyroidism ; Infant ; Infant, Newborn ; Male ; Mutation, Missense ; Parathyroid Hormone ; Receptors, Virus
[en] 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. © 2013 The American Society of Human Genetics.
http://hdl.handle.net/10993/27300
10.1016/j.ajhg.2013.04.020

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