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Mutations in the RUNX2 gene in patients with cleidocranial dysplasia
Author(s) -
Otto Florian,
Kanegane Hirokazu,
Mundlos Stefan
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10043
Subject(s) - cleidocranial dysplasia , missense mutation , biology , genetics , runx2 , locus (genetics) , short stature , nonsense mutation , gene , phenotype , transcription factor , anatomy , supernumerary , endocrinology
Cleidocranial dysplasia (CCD) is a autosomal dominant disorder characterized by skeletal anomalies such as patent fontanels, late closure of cranial sutures with Wormian bones, late erupting secondary dentition, rudimentary clavicles, and short stature. The locus for this disease was mapped to chromosome 6p21. RUNX2 is a member of the runt family of transcription factors and its expression is restricted to developing osteoblasts and a subset of chondrocytes. Mutations in the RUNX2 gene have been shown to cause CCD. Chromosomal translocations, deletions, insertions, nonsense and splice‐site mutations, as well as missense mutations of the RUNX2 gene have been described in CCD patients. Although there is a wide spectrum in phenotypic variability ranging from primary dental anomalies to all CCD features plus osteoporosis, no clear phenotype–genotype correlation has been established. However analysis of the three‐dimensional structure of the DNA binding runt domain of the RUNX proteins and its interaction with DNA, as well as the cofactor CBFB, start to provide an insight into how missense mutations affect RUNX2 function. Hum Mutat 19:209–216, 2002. © 2002 Wiley‐Liss, Inc.