摘要：

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder exhibiting a wide clinical spectrum ranging from minimal anomalies to classic CCD. Mutations scattered throughout the entire CBFA1 gene have been related to this disorder. However, it seems that most of them affect the highly conserved Runt domain, abolishing the DNA-binding ability of this transcription factor. Moreover, no systematic effect has been found to relate the type of mutation to the severity of the clinical features. In this paper, we studied two unrelated patients with classic CCD. DNA analysis revealed two novel mutations and three undescribed polymorphisms. One of the substitutions was a missense mutation in the Q/A domain leading to the replacement of a polar residue by a nonpolar one (158 A → T [Q53L]). The second was an uncommon heterozygous stop codon mutation (1565 G → C [X522S]) which theoretically results in a longer protein with 23 additional amino acids. This is the first report of this type of mutation in CBFA1 . We discuss the possible consequences of these mutant sequences, although no phenotype–genotype correlation could be established. Our findings expand the existing number of allelic variants in this pathology.

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