Rabbit Anti-Human CNOT2 Polyclonal Antibody

Only a few individuals with 12q15 deletion have been described, presenting with a disorder characterized by learning disability, developmental delay, nasal speech, and hypothyroidism. The smallest region of overlap for this syndrome was included in a genomic segment spanning CNOT2, KCNMB4, and PTPRB genes. We report on an additional patient harboring a 12q15 microdeletion encompassing only part of CNOT2 gene, presenting with a spectrum of clinical features overlapping the 12q15 deletion syndrome phenotype. We propose CNOT2 as the phenocritical gene for 12q15 deletion syndrome and its haploinsufficiency being associated with an autosomal dominant disorder, presenting with developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphisms.

Chromosome 12q15 microdeletion syndrome is characterized by intellectual disability and dysmorphic facial features, but the associations between each of the deleted genes and the phenotypes of 12q15 microdeletion syndrome remain unclear. Recently, the smallest region of overlap in 16 previously reported patients was used to define three candidate genes for the 12q15 microdeletion syndrome: CNOT2, KCNMB4, and PTPRB. Among these three candidate genes, CNOT2 maintains the structural integrity of the carbon catabolite repressor 4 (CCR4)-negative on TATA (NOT) complex, which plays a key role in regulating global gene expression, and is essential for the enzymatic activity of the CCR4-NOT complex. Disruption of the CCR4-NOT complex results in dysregulation of global gene expression, and is associated with various human disease processes, including neuronal diseases. Therefore, CNOT2 haploinsufficiency might account for the neurological features of the 12q15 microdeletion syndrome. Herein, we document a 12-year-old female patient with mild intellectual disability and multiple structural abnormalities including cleft lip and palate and 2-3 toe syndactyly. She exhibited dysmorphic facial features such as upslanting and short palpebral fissures, micrognathia, low-set ears, and hypoplastic antihelix. A microarray analysis showed a de novo 1.32-Mb deletion within 12q15 that included CNOT2 and 14 other genes. Remapping of the 12q15 deletion region in the 16 previously reported patients together with that in the newly identified patient indicated that CNOT2 is the only gene that is commonly deleted. These findings suggest that CNOT2 is the prime candidate for the neurological phenotypes of the 12q15 microdeletion syndrome.