Article (Scientific journals)
FAM111A mutations result in hypoparathyroidism and impaired skeletal development
Unger, Sheila; Górna, Maria W.; Le Béchec, Antony et al.
2013In American Journal of Human Genetics, 92 (6), p. 990-995
Peer reviewed
 

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Keywords :
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
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
eid=2-s2.0-84878878820
Author, co-author :
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
More authors (14 more) Less
External co-authors :
yes
Language :
English
Title :
FAM111A mutations result in hypoparathyroidism and impaired skeletal development
Publication date :
2013
Journal title :
American Journal of Human Genetics
ISSN :
0002-9297
Volume :
92
Issue :
6
Pages :
990-995
Peer reviewed :
Peer reviewed
Available on ORBilu :
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