Six novel mutations of the RUNX2 gene in Italian patients with cleidocranial dysplasia.
We report clinical and molecular findings in 14 patients with cleidocranial dysplasia (CCD), a well defined skeletal disorder with characteristic clinical findings and autosomal dominant inheritance. We identified ten heterozygous base changes in the RUNX2 gene, including six novel mutations [c.522insA, c.389G>A (W130X), c.662T>G (V221G), IVS2+T>A, c.1111_1129del19, and c.873_874delCA]. We did not establish a clear correlation between clinical features and genotype, the phenotypes of all patients analyzed falling within the range of variation described in CCD without an effect related to the length of the predicted protein. In two cases, however, a limb-girdle myopathy affecting the shoulder muscles was also identified. Our data add new variants to the repertoire of RUNX2 mutations in CCD.
Tessa
Alessandra
A
Molecular Medicine and Genetics, IRCCS-Bambino Gesù, Rome, Italy.
Salvi
Sergio
S
Casali
Carlo
C
Garavelli
Livia
L
Digilio
M Cristina
MC
Dotti
M Teresa
MT
Di Giandomenico
Silvia
S
Valoppi
Manuela
M
Grieco
Gaetano S
GS
Comanducci
Giovanna
G
Bianchini
Giacomo
G
Fortini
Daniela
D
Federico
Antonio
A
Giannotti
Aldo
A
Santorelli
Filippo M
FM
D019943:Amino Acid Substitution / Q000235:genetics; D002478:Cells, Cultured; D002973:Cleidocranial Dysplasia / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D014157:Transcription Factors