Lo Muzio Lorenzo, Tetè Stefano, Mastrangelo Filiberto, Cazzolla Angela Pia, Lacaita Maria Grazia, Margaglione Maurizio, Campisi Giuseppina
Department of Surgical Sciences, University of Foggia, Foggia, Italy.
Ann Clin Lab Sci. 2007 Spring;37(2):115-20.
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells into osteoblasts and is essential for membranous as well as endochondral bone formation. In this study of a 14-yr-old boy with typical CCD phenotype, the authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segments from the patient's CBFA1/RUNX2 gene were identical to those obtained in controls, except for the one spanning the exon 7 and intron/exon boundary regions. Direct sequencing of the PCR product showed a heterozygous T-to-A transition mutation at nucleotide 1182 in exon 7, leading to Y394X mutation. The predicted protein product lacks 128 amino acids, including part of the PST domain. Identification of this novel mutation constitutes a further step in elucidating the pathogenesis of this autosomal disorder.
锁骨颅骨发育不全（CCD）是一种常染色体显性遗传性骨骼发育不良疾病，其特征为锁骨异常、颅缝和囟门未闭合、多生牙、身材矮小以及其他多种骨骼变化。致病基因是CBFA1/RUNX2，定位于6号染色体p21区域。CBFA1/RUNX2基因因突变而失活与CCD患者出现的骨骼缺陷有关。CBFA1/RUNX2控制前体细胞向成骨细胞的分化，对膜内成骨和软骨内成骨均至关重要。在这项对一名具有典型CCD表型的14岁男孩的研究中，作者发现了一种新的CBFA1/RUNX2基因突变。患者CBFA1/RUNX2基因的所有扩增片段与对照样本的扩增片段均相同，只有跨越外显子7和内含子/外显子边界区域的片段除外。对PCR产物进行直接测序显示，外显子7中第1182位核苷酸发生了杂合性T到A的转换突变，导致Y394X突变。预测的蛋白质产物缺少128个氨基酸，包括部分PST结构域。鉴定出这种新突变是阐明这种常染色体疾病发病机制的又一进展。
