Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism

Ren, Congmian; Liang, Yan; Wei, Fengxiang; Zhang, Yanan; Zhong, Shouqiang; Gu, Heng; Dong, Xingsheng; Huang, Yuguang; Ke, Hua Zhu; Son, Xin-ming; Tang, Damu; Chen, Zheng

doi:10.1016/j.bbadis.2012.11.009

Cited by 15 publications

(12 citation statements)

References 26 publications

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“…Moreover, it was reported that missense mutations in ZNF407 affect tumor progression, as evidenced by whole-genome sequencing of gastrointestinal stromal tumors. 28 Moreover, our functional studies of ZNF407 showed that ZNF407 functioned as a promotive factor in CRC metastasis and accelerated cell proliferation slightly (Supplementary Figure S3). Together, these data suggest a novel theory that CRC metastasis is regulated by WDR5.…”

Section: Discussionmentioning

confidence: 92%

“…More importantly, molecular studies revealed that WDR5-transfected cells underwent EMT and were modulated by the PI3K/AKT signaling pathway. Furthermore, gene expression microarrays were used to identify ZNF407, which was reported to affect tumor progression, 27, 28 as a novel target of WDR5, which markedly increased CRC cell migration. Thus, we propose that WDR5 is a promising target in CRC prognostics and therapeutics.…”

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confidence: 99%

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PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407

Tan

Chen

et al. 2017

Cell Death Dis

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Colorectal cancer (CRC) is the third most common cause of cancer deaths, and has a high rate of liver and lung metastasis. Unfortunately, distant metastasis is the main barrier for advanced CRC therapy and leads to a very low survival rate. In this study, we identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for CRC patients. We demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo. In an effort to investigate the impact of WDR5 on CRC cell fate, we treated CRC cells with growth factor and inhibitor. We report that WDR5 is a novel factor in the metastasis of CRC by triggering epithelial–mesenchymal transition (EMT) process in response to the PI3K/AKT signaling pathway. Moreover, WDR5 shows a direct binding to the ZNF407 promoter on regulating cellular EMT process, leading to CRC metastasis. Hence, our findings strongly position WDR5 as a valuable marker for CRC, and inhibiting WDR5 or the associated signaling pathways may be an effective strategy for the future development of anti-CRC therapy.

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Section: Discussionmentioning

confidence: 92%

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confidence: 99%

PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407

Tan

Chen

et al. 2017

Cell Death Dis

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“…Aural atresia is caused by hemizygosity of the TSHZ1 gene (Feenstra et al, 2011). Hemizygosity of several genes have been implicated in cognitive abilities, ZNF407 (Ren et al, 2013) and NETO1 (Ng et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Establishing a reference group for distal 18q-: clinical description and molecular basis

Cody¹,

Hasi

Soileau

et al. 2013

Hum Genet

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Although constitutional chromosome abnormalities have been recognized since the 1960s, clinical characterization and development of treatment options have been hampered by their obvious genetic complexity and relative rarity. Additionally, deletions of 18q are particularly heterogeneous, with no two people having the same breakpoints. We identified sixteen individuals with deletions that, despite unique breakpoints, encompass the same set of genes within a 17.6 Mb region. This group represents the most genotypically similar group yet identified with distal 18q deletions. As the deletion is of average size when compared with other 18q deletions, this group can serve as a reference point for the clinical and molecular description of this condition. We performed a thorough medical record review as well as a series of clinical evaluations on 14 of the 16 individuals. Common functional findings included developmental delays, hypotonia, growth hormone deficiency, and hearing loss. Structural anomalies included foot anomalies, ear canal atresia/stenosis, and hypospadias. The majority of individuals performed within the low normal range of cognitive ability but had more serious deficits in adaptive abilities. Of interest, the hemizygous region contains 38 known genes, 26 of which are sufficiently understood to tentatively determine dosage sensitivity. Published data suggest that 20 are unlikely to cause an abnormal phenotype in the hemizygous state and five are likely to be dosage sensitive: TNX3, NETO1, ZNF407, TSHZ1, and NFATC. A sixth gene, ATP9B, may be conditionally dosage sensitive. Not all distal 18q- phenotypes can be attributed to these six genes; however, this is an important advance in the molecular characterization of 18q deletions.

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“…Analysis of several CAA patients led to defining the breakpoint of the deletion within ZNF407 [24] . Another identified translocation breakpoint in the third intron of the ZNF407 gene causes a reduction in the transcript of its isoform 1, resulting in non-syndromic intellectual impairment and autism [25]. Furthermore, two de novo damaging missense mutations [c.A1436G/p.Y460C; c.C3640G/p.P1195A] in the very long linker region between zinc fingers 3 and 4, and between 11 and 12, respectively, of the ZNF407 gene were found in one intellectual impairment patient each.…”

Section: Discussionmentioning

confidence: 99%

Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive cognitive impairment syndrome

Kambouris

Maroun

Ben‐Omran

et al. 2014

Orphanet J Rare Dis

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BackgroundA consanguineous Arab family is affected by an apparently novel autosomal recessive disorder characterized by cognitive impairment, failure-to-thrive, hypotonia and dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally.MethodsThe family was studied by homozygosity mapping, candidate gene mutation screening and whole Exome Next Generation Sequencing of a single affected member to identify the offending gene and mutation. The mutated gene product was studied by structural bioinformatics methods.ResultsA damaging c.C5054G mutation affecting an evolutionary highly conserved amino acid p.S1685W was identified in the ZNF407 gene at 18q23. The Serine to Tryptophane mutation affects two of the three ZNF407 isoforms and is located in the last third of the protein, in a linker peptide adjoining two zinc-finger domains. Structural analyses of this mutation shows disruption of an H-bond that locks the relative spatial position of the two fingers, leading to a higher flexibility of the linker and thus to a decreased probability of binding to the target DNA sequence essentially eliminating the functionality of downstream domains and interfering with the expression of various genes under ZNF407 control during fetal brain development.ConclusionsZNF407 is a transcription factor with an essential role in brain development. When specific and limited in number homozygosity intervals exist that harbor the offending gene in consanguineous families, Whole Exome Sequencing of a single affected individual is an efficient approach to gene mapping and mutation identification.

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Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism

Cited by 15 publications

References 26 publications

PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407

PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407

Establishing a reference group for distal 18q-: clinical description and molecular basis

Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive cognitive impairment syndrome

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