CNOT2 as the critical gene for phenotypes of 12q15 microdeletion syndrome

Tomoko Uehara, Toshiki Takenouchi, Yu Yamaguchi, Yumi Daimon, Hisato Suzuki, Yuri Sakaguchi, Kenjiro Kosaki

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Phenotype
Carbon
Genes
Intellectual Disability
Micrognathism
Syndactyly
Multiple Abnormalities
Gene Expression
Haploinsufficiency
Cleft Lip
Cleft Palate
Toes
Eyelids
Microarray Analysis
Ear
Chromosomes

Keywords

  • chromosome 12q15
  • CNOT2
  • developmental delay
  • intellectual disability
  • nasal voice

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

CNOT2 as the critical gene for phenotypes of 12q15 microdeletion syndrome. / Uehara, Tomoko; Takenouchi, Toshiki; Yamaguchi, Yu; Daimon, Yumi; Suzuki, Hisato; Sakaguchi, Yuri; Kosaki, Kenjiro.

In: American Journal of Medical Genetics, Part A, 01.01.2019.

Research output: Contribution to journalArticle

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