Cryptic microdeletion of the CREBBP gene from t(1;16) (p36.2;p13.3) as a novel genetic defect causing Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RTS) is a multiple congenital anomaly syndrome characterized by facial abnormalities, broad thumbs and toes, and mental retardation. RTS is known to be caused by the disruption, either by point mutations or microdeletions, of the human CREB-binding protein (CREBBP) gene on 16p13.3. Gross rearrangements involving 16p13.3, such as translocations or inversions, have rarely been reported in RTS. A 3-month-old boy with a phenotype typical of RTS was referred for genetic diagnosis. Cytogenetic analysis revealed a novel reciprocal translocation: t(1;16)(p36.2;p13.3). Gene dosage analysis for the CREBBP gene was performed using multiple ligation-dependent probe amplification (MLPA) and revealed heterozygous deletion of the whole CREBBP gene. Genome-wide single nucleotide polymorphism (SNP)-array confirmed the deletion and also indicated large genomic deletions in both 1p36.2 and 16p13.3. To the best of our knowledge, this is the first report of characterization of the genomic dosage imbalances in RTS by SNP-array.