A novel CREBBP mutation and its phenotype in a case of Rubinstein–Taybi syndrome

Wang, Qian; Wei, Wen Bin; Rong, Wei Ning; Shi, Xiang Yu

doi:10.1186/s12920-022-01335-4

Cited by 5 publications

(4 citation statements)

References 48 publications

(97 reference statements)

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“…The CREBBP gene influences CREB-binding proteins that play a role in regulating the activity of various genes in tissues throughout the body ( Cardinaux et al, 2000 ; Gao et al, 2020 ). Previous studies have shown that the CREBBP-binding proteins are involved in brain development and long-term memory formation ( Chatterjee et al, 2020 ; Wang et al, 2022 ). CREBBP gene may play a role in the pathogenesis of various neurodegenerative diseases, such as HD ( Steffan et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

Belkozhayev,

Niyazova,

Kamal

et al. 2024

Front. Cell. Neurosci.

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Huntington’s disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD.

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Section: Discussionmentioning

confidence: 99%

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

Belkozhayev,

Niyazova,

Kamal

et al. 2024

Front. Cell. Neurosci.

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“…12,13 The hereditary condition RSTS is linked to mutations in CREBBP and is characterized by ID and developmental delays. 14 The mutations detected in RSTS patients range from point mutations to microdeletions eliminating the entire gene, leading to the haploinsufficiency of this dosage-sensitive gene. 15 More specifically, studies of individuals with missense and splice-site mutations in the CREBBP HAT domain revealed that loss of HAT activity is sufficient to cause the ID syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…It plays a role in complexes that remodel chromatin, affects development, and aids in the control of genes through epigenetic mechanisms 12,13 . The hereditary condition RSTS is linked to mutations in CREBBP and is characterized by ID and developmental delays 14 . The mutations detected in RSTS patients range from point mutations to microdeletions eliminating the entire gene, leading to the haploinsufficiency of this dosage‐sensitive gene 15 .…”

Section: Introductionmentioning

confidence: 99%

Molecular insight into CREBBP and TANGO2 variants causing intellectual disability

Hussain,

Muhammad,

Khan

et al. 2023

The Journal of Gene Medicine

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BackgroundIntellectual disability (ID) can be associated with different syndromes such as Rubinstein‐Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB‐binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2‐related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Clinicians need more clinical and genetic evidence to detect and comprehend the phenotypic spectrum of this disorder.MethodsExome sequencing was used to identify the disease‐causing variants in two affected families A and B from District Kohat and District Karak, Khyber Pakhtunkhwa. Affected individuals from both families presented symptoms of ID, developmental delay and behavioral abnormalities. The validation and co‐segregation analysis of the filtered variant was carried out using Sanger sequencing.ResultsIn the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP_004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605 + 1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild‐type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function.ConclusionsRSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype–phenotype associations.

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“…Therefore, a reasonable and effective assessment of managing financial risks and studying risk linkages and spillover effects among financial markets are beneficial for regulators to track and control the risks of each financial market in a timely manner [6][7][8][9]. This allows a better grasp of the direction of financial risks and is important for promoting stable and healthy economic development [10][11][12][13][14]. Therefore, in the context of globalization, how to effectively assess and manage risks is gradually drawing the attention of financial market regulators and practitioners [15].…”

Section: Introductionmentioning

confidence: 99%

Financial risk assessment management of cloud accounting SOEs based on spillover index

Zhao

2023

Applied Mathematics and Nonlinear Sciences

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The international capital flows between the financial markets of state-owned enterprises are frequent and closely linked, and the difficulty of assessing and managing risks is deepening day by day. In order to be able to provide some useful references for corporate financial institutions in theory and practice, this paper is oriented to cloud accounting SOEs, modeling and calculating SOE returns and volatilities to obtain corporate financial spillover indices. The calculated spillover index is introduced into the basic assessment system to establish the financial risk assessment system. Based on the expert scoring results of the assessment indexes, a judgment matrix is constructed to obtain the fuzzy assessment weights of each index. Combined with the system assessment results, the risk matrix is used to classify risk levels and develop corresponding management strategies. It is experimentally verified that the intensity of the total risk spillover index and the probability of risk occurrence between different submarkets of corporate finance are higher during the unpracticed period, 76% and 83.48%, respectively. In contrast, the spillover index intensity and the probability of risk occurrence in the practice period are only 50% and 61.15%. This shows that the proposed method can carry out effective risk assessment management based on the spillover index, which meets the needs of the times and realistic needs of cloud accounting SOEs for financial risk assessment management and promotes the financial business development of SOEs.

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A novel CREBBP mutation and its phenotype in a case of Rubinstein–Taybi syndrome

Cited by 5 publications

References 48 publications

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

Differential microRNA expression in the SH-SY5Y human cell model as potential biomarkers for Huntington’s disease

Molecular insight into CREBBP and TANGO2 variants causing intellectual disability

Financial risk assessment management of cloud accounting SOEs based on spillover index

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