Reviews
Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome and Novel Insights Underlying the Phenotypic Continuum of CSNK2B …
… Upon the overexpression of CSNK2A1 with either the wild-type or mutant CSNK2B construct… These data support the haploinsufficiency as an underlying pathomechanism in our patient. …
Publication: M Di Stazio, C Zanus, F Faletra, A Pesaresi, I Ziccardi… - Genes, 2023 - mdpi.com
This study presents case-level genetic evidence indicating CK2beta haploinsufficiency as pathogenic, with two patients exhibiting distinct loss-of-function (LoF) mutations: Patient 1 with missense mutation p.Leu39Arg with dysmorphic features but unknown inheritance, and Patient 2 with a frameshift mutation Met132fs showing a significant reduction in CSNK2B mRNA expression and stability. Functional studies support haploinsufficiency, demonstrating reduced protein interaction and enzymatic activity, a significant decrease in mRNA expression and protein stability, and a likely destabilizing effect on protein structure due to altered amino acid spatial orientation. In silico predictions and comparative analysis of multiple mutations suggest a common pathogenetic mechanism involving LoF, reinforced by qRT-PCR and protein expression analysis. These findings underscore CK2beta's critical role in the observed disease phenotypes.
Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion
… -mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism… patient, individuals with CSNK2A1 null variants showed a clinical profile similar to our patient's …
Publication: H Nan, M Chu, J Zhang, D Jiang… - Molecular Genetics & …, 2024 - Wiley Online Library
The dataset presents clinical and genetic evidence for CSNK2A1 haploinsufficiency impacting human disease, characterized through mutations in various patients indicating loss of function (LoF). Multiple cases depicted the presence of null or LoF mutations: Proband with 'c.967dupT, p.Tyr323Leufs*16', exhibiting developmental delays and other phenotypic abnormalities; Patient 26 encompassing 'p.R191*' mutation, phenotype unspecified; Patient 28 with 'c.1061-1G > C' splice variant, phenotype not detailed; Proband with p.Tyr323Leufs*16 variant, linked to seizures and limb weakness; Patient with 'p.H29Cfs*9', experiencing fewer neurodevelopmental concerns; and Patient with start codon mutation 'p.M1V', clinical profile not detailed, inheritance information unavailable for the last two. Functional studies employing transcription and gene expression analysis revealed reduced CSNK2A1 product or mRNA, consistent with haploinsufficiency and suggesting decreased protein levels due to nonsense-mediated decay in the case of the frameshift variant.
De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features
We present five patients with neurodevelopmental disabilities and dysmorphic features in whom we identified five different de novo novel variants in CSNK2A1.
Publication: Hum Genet
This study presented evidence for haploinsufficiency of the CSNK2A1 gene in association with neurodevelopmental disabilities and dysmorphic features. Five patients were identified to harbor novel, de novo heterozygous variants, including one splice site variant (c.824+2T>C) and four missense variants (p.R47Q, p.Y50S, p.D175G, p.K198R), which are predicted to be deleterious by in silico models such as SIFT, Mutation Taster, Provean, and CADD. Clinical phenotypes of these patients prominently featured neurodevelopmental delays and dysmorphic facial features, with most patients exhibiting additional symptoms such as intellectual disability, behavioral problems, hypotonia, speech and gastrointestinal problems, with a subset also manifesting microcephaly, pachygyria, musculoskeletal, and immunologic issues. These variants were confirmed as de novo and inheritance testing was performed, indicating their likely contribution to the disease phenotype. Complementary functional studies in animal models, specifically conditional CK2α knock-out mice, demonstrated embryonic lethality and severe abnormalities when homozygous, and a 13% incidence of neural tube closure failure in heterozygous embryos, supporting the hypothesis that CSNK2A1 haploinsufficiency plays a significant role in human developmental disorders.
Genetic testing in a cohort of patients with potential epilepsy with myoclonic-atonic seizures
While EMAS is widely accepted to have a strong genetic component, the diagnostic yield of genetic testing remains low.
Publication: Epilepsy Research
In a study focusing on CSNK2A1's role in human disease, whole exome sequencing identified a de novo, likely pathogenic intronic variant in CSNK2A1 in an eight-year-old female presenting with myoclonic and tonic seizures with onset in infancy, along with mild cognitive and language delays. The intronic mutation is predicted to cause abnormal gene splicing, leading to CSNK2A1 haploinsufficiency. Clinical phenotype improvement was noted with seizure response to felbamate and consequently significant cognitive and language development. The mutation is characterized as being de novo with tested inheritance, further supporting the link between the CSNK2A1 variant and the observed phenotype. No functional studies are reported in the dataset, leaving a gap in the direct assessment of the variant's impact on protein function or gene expression.
Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures
… that a de novo CSNK2A1 variant was the most-plausible causative variant in this patient. On the … Therefore, CSNK2B haploinsufficiency is the pathomechanism in these patients. Our …
Publication: M Nakashima, J Tohyama, E Nakagawa… - Journal of human …, 2019 - nature.com
In this study, the functional implications of CSNK2A1 haploinsufficiency in human disease were analyzed by examining clinical phenotypes and performing functional studies on patients carrying loss-of-function mutations. The evidence was derived from two patients: Patient 1 with a missense variant (CSNK2A1 NM_177559.2:c.593A>G, p.(Lys198Arg)) and Patient 2 with a nonsense mutation (CSNK2A1 NM_177559.2:c.571C>T, p.Arg191*). Patient 1 exhibited a clinical phenotype including global developmental delays, hypotonia, intractable seizures, and additional severe manifestations such as respiratory failure, without inheritance information available. Patient 2 presented with a phenotype resembling Dravet syndrome, similarly showing global developmental delays and intractable seizures, and deceased at 1 year and 7 months; inheritance was tested but the transmission pattern is not specified. Functional studies employing HEK293T cells elucidated the interaction between CSNK2A1 and CSNK2B proteins, with one variant showing no interaction, suggesting a role in CK2 holoenzyme instability. Another study indicated a wild type and a specific mutant CSNK2B interaction comparable to CSNK2A1, implying the variant does not impact the interaction. These cellular analyses, alongside discussions on the functional impact on CK2α, supported the gene-disease association related to CSNK2A1 haploinsufficiency.
Two novel CSNK2A1 variants associated with mild Okur-Chung neurodevelopmental syndrome phenotype
In this report, we expand the genotypic spectrum of OCNDS by reporting two novel CSNK2A1 variants, identified in two children by whole exome sequencing (WES). Both patients have African ancestors. They present with distinct, non-overlapping, subtle phenotypes, emphasizing the wide clinical variability associated with this condition.
Publication: Clinical Dysmorphology
This compilation of clinical genetic evidence focuses on the CSNK2A1 gene and its role in disease through haploinsufficiency. Two patients were investigated for their clinical phenotypes associated with frameshift and missense variants identified by sequencing technologies. Patient 1 exhibits a de novo CSNK2A1 frameshift variant leading to significant failure to thrive and behavioral feeding problems, with no associated learning difficulties or confirmed inheritance due to testing not performed. Additionally, a missense variant (NM_177559.3:c.142G>A (p.Gly48Ser)) in the same patient correlates with inattention and lack of academic focus; inheritance was confirmed as de novo. In the second case, a frameshift variant (p.(His29CysfsTer9)) involves generalized tonic-clonic seizures, coordination difficulties, and normal speech acquisition; the inheritance is confirmed as de novo. Another report on patient 1, possibly a different clinical manifestation or an incomplete dataset, describes a heterozygous frameshift variant (NM_177559.3:c.85_86delCA) causing seizures and motor delay, with inheritance information unavailable. For patient 2, the same frameshift mutation is noted, presenting notably with seizures and no distinctive features, and also without inheritance information. Functional studies are lacking, making it difficult to assert the exact impact of variants on protein function, but multiple cases indicate predicted loss-of-function as key findings supporting haploinsufficiency of CSNK2A1.
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Two novel CSNK2A1 variants associated with mild Okur-Chung neurodevelopmental syndrome phenotype
In this report, we expand the genotypic spectrum of OCNDS by reporting two novel CSNK2A1 variants, identified in two children by whole exome sequencing (WES). Both patients have African ancestors. They present with distinct, non-overlapping, subtle phenotypes, emphasizing the wide clinical variability associated with this condition.
Publication: Clinical Dysmorphology
Genetic testing in a cohort of patients with potential epilepsy with myoclonic-atonic seizures
While EMAS is widely accepted to have a strong genetic component, the diagnostic yield of genetic testing remains low.
Publication: Epilepsy Research
De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features
We present five patients with neurodevelopmental disabilities and dysmorphic features in whom we identified five different de novo novel variants in CSNK2A1.
Publication: Hum Genet
Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome and Novel Insights Underlying the Phenotypic Continuum of CSNK2B …
… Upon the overexpression of CSNK2A1 with either the wild-type or mutant CSNK2B construct… These data support the haploinsufficiency as an underlying pathomechanism in our patient. …
Publication: M Di Stazio, C Zanus, F Faletra, A Pesaresi, I Ziccardi… - Genes, 2023 - mdpi.com
Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures
… that a de novo CSNK2A1 variant was the most-plausible causative variant in this patient. On the … Therefore, CSNK2B haploinsufficiency is the pathomechanism in these patients. Our …
Publication: M Nakashima, J Tohyama, E Nakagawa… - Journal of human …, 2019 - nature.com
Two novel CSNK2A1 variants associated with mild Okur-Chung neurodevelopmental syndrome phenotype
… Nevertheless, it seems that several individuals with CSNK2A1 loss of functional alterations, including deletions, were shown to have a clinical picture resembling our patient’s natural …
Publication: M Wafik, H Kuoppamaa, P Hirani, J Hignett… - Clinical …, 2023 - journals.lww.com
Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion
… -mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism… patient, individuals with CSNK2A1 null variants showed a clinical profile similar to our patient's …
Publication: H Nan, M Chu, J Zhang, D Jiang… - Molecular Genetics & …, 2024 - Wiley Online Library
De Novo CSNK2B Mutations in Five Cases of Poirier–Bienvenu Neurodevelopmental Syndrome
… stimulation test, and the results revealed that patient 3 showed partial GH deficiency and patient 4 showed complete GH deficiency. Patient 4 underwent rhGH treatment for 3 years and …
Publication: Q Yang, Q Zhang, S Yi, Z Qin, F Shen, S Ou… - Frontiers in …, 2022 - frontiersin.org
Genetic analysis and literature review of a Poirier–Bienvenu neurodevelopmental syndrome family line caused by a de novo frameshift variant in CSNK2B
… However, the efficacy of anti-epileptic treatment varies depending on the type of genetic variant, the type of seizure, and the severity of the patient's condition. CSNK2B is located at 6p21…
Publication: D Li, B Zhou, X Tian, X Chen, Y Wang… - … Genetics & Genomic …, 2024 - Wiley Online Library
De novo variants of CSNK2B cause a new intellectual disability-craniodigital syndrome by disrupting the canonical Wnt signaling pathway
… was adopted; due to phenotypic overlap of patient 1 with Filippi syndrome, we first excluded … Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental …
Publication: M Asif, E Kaygusuz, M Shinawi, A Nickelsen… - Human Genetics and …, 2022 - cell.com
6p21. 33 Deletion encompassing CSNK2B is associated with relative macrocephaly, facial dysmorphism, and mild intellectual disability
… haploinsufficiency could account for our patient’s features. … recessive disease and lead to haploinsufficiency of a number of … Our results indicate that CSNK2B haploinsufficiency plays a …
Publication: I Ohashi, Y Kuroda, Y Enomoto, H Murakami… - Clinical …, 2021 - journals.lww.com
CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity
… De novo variants in CSNK2A1, encoding the α subunit, cause a condition characterized by … The heterozygous predicted LoF variants in our patients suggest a haploinsufficiency …
Publication: ME Ernst, EH Baugh, A Thomas, L Bier, N Lippa… - …, 2021 - Wiley Online Library
Refining the clinical phenotype of Okur–Chung neurodevelopmental syndrome
… missense mutation in CSNK2A1, c.… patient’s phenotype, especially ID and synophrys, is similar to that of Kleefstra syndrome. Kleefstra syndrome can be caused by a haploinsufficiency …
Publication: M Akahira-Azuma, Y Tsurusaki, Y Enomoto… - Human Genome …, 2018 - nature.com
Persistent hyperplastic primary vitreous with microphthalmia and coloboma in a patient with okur-chung neurodevelopmental syndrome
… an OCNDS patient with a novel CSNK2A1 nonsense variant … CSNK2A1 haploinsufficiency and ocular phenotypes. The accumulation of future cases may clarify the role of CSNK2A1 in …
Publication: H Murakami, T Uehara, Y Enomoto… - Molecular …, 2022 - karger.com
Germline de novo variants in CSNK2B in Chinese patients with epilepsy
… haploinsufficiency score (%HI) of 5.78 (DECIPHER), indicating that it is extremely LoF intolerant and likely to exhibit haploinsufficiency. … monotherapy (patient 5 and 8 with LEV, patient 6 …
Publication: J Li, K Gao, S Cai, Y Liu, Y Wang, S Huang, J Zha… - Scientific reports, 2019 - nature.com
Are CSNK2A1 gene mutations associated with retinal dystrophy? Report of a patient carrier of a novel de novo splice site mutation
… CSNK2A1 haploinsufficiency may be a disease-causing mechanism [8]. In conclusion, we here report a patient … a de novo mutation in the CSNK2A1 gene. Future genotype–phenotype …
Publication: D Colavito, E Del Giudice, C Ceccato… - Journal of Human …, 2018 - nature.com
Transcriptome Analysis of Severe Congenital Neutropenia Associated Leukemia with Different Types of RUNX1 Mutations in an iPSC-Based Model
… P-value < 0.05) genes between CN/AML and CN stages for CN patient 1 and CN patient 2, … ) with missense RUNX1 mutation and RUNX1 haploinsufficiency, we found motifs for GATA1, …
Publication: B Dannenmann, B Oswald, MU Ritter, M Nasri… - Blood, 2020 - Elsevier
Program Areas
… The two scientific workshops brought together scientists who study the CSNK2A1 and … studies, and they will expedite the creation of patient-derived induced pluripotent stem cells (iPSCs…
Publication: J Sills, W Chung, V Okur - sfari.org
Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia
… (Patients 2–4) but not in IKZF1 haploinsufficiency (Patient 1). d Activity of the MTOR promoter (−1 … We tested whether IKZF1 haploinsufficiency affects IKAROS’s ability to regulate MTOR …
Publication: Z Ge, C Song, Y Ding, BH Tan, D Desai, A Sharma… - Leukemia, 2021 - nature.com
Dissection of mendelian predisposition and complex genetic architecture of craniovertebral junction malformation
… in genes associated with Mendelian diseases, including CSNK2A1, MSX2, and DDX3X. In … infer that the haploinsufficiency of MSX2 caused the observed CVJ defects in our patient by …
Publication: Z Liu, H Du, H Zhao, S Cai, S Zhao, Y Niu, X Li, B Liu… - Human Genetics, 2023 - Springer
De novo ZBTB7A variant in a patient with macrocephaly, intellectual disability, and sleep apnea: implications for the phenotypic development in 19p13.3 …
… 1), suggesting that haploinsufficiency of MAP2K2 involved in the Ras/MAPK pathway is the … They have also noted a clinical overlap between MAP2K2 haploinsufficiency and MAP2K2 …
Publication: A Ohishi, Y Masunaga, S Iijima, K Yamoto… - Journal of human …, 2020 - nature.com
Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations
… 1q21.1 was identified; haploinsufficiency of gene SF3B4 in 1q21.1 … only in SNRPB and CSNK2A1 have been reported to be … supporting their pathogenicity in haploinsufficiency. In case …
Publication: C Xu, Y Xiang, X Xu, L Zhou, H Li, X Dong… - Molecular Cytogenetics, 2020 - Springer
Novel Roles for ANKS1B in the Pathogenesis of Neurodevelopmental Disorders
… of Anks1b haploinsufficiency recapitulates a range of patient … Our mouse model of Anks1b haploinsufficiency had a synaptic … of diverse etiology, including ANKS1B haploinsufficiency. …
Publication: AU Carbonell - 2020 - search.proquest.com
Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations
… might arise due to dosage sensitivity (haploinsufficiency) whereas the other might result from … other ASD proband shared a missense variant in CSNK2A1 with a schizophrenia proband (…
Publication: E Rees, HDJ Creeth, HG Hwu, WJ Chen… - Nature …, 2021 - nature.com
Doctor of Clinical Sciences
… to-date disease association information and haploinsufficiency scores we generated a shortlist … CNL and showed that haploinsufficiency of ATP6V0C probably underlies the pathology of …
Publication: GJ Burghel - 2021 - pure.manchester.ac.uk
Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses
… , and the phenotype of the proband does not comprise spastic … in CSNK2B result in haploinsufficiency, leading to early-… in this proband results in haploinsufficiency of CSNK2B, and …
Publication: G Demidov, B Yaldiz, J Garcia-Pelaez, E de Boer… - medRxiv, 2023 - medrxiv.org
De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis
… Exome sequencing of trios with syndromic CS To systematically identify genetic causes of syndromic CS, we ascertained 555 proband-parent trios who had undergone genetic …
Publication: AT Timberlake, S McGee, G Allington, E Kiziltug… - The American Journal of …, 2023 - cell.com
Transcription factor protein interactomes reveal genetic determinants in heart disease
… the results with nearly 9,000 exomes from proband-parent trios revealed an enrichment of de … Scoring variants of interactome members based on residue, gene, and proband features …
Publication: B Gonzalez-Teran, M Pittman, F Felix, R Thomas… - Cell, 2022 - cell.com
Prevalence and architecture of de novo mutations in developmental disorders
… DNMs per proband is higher than … haploinsufficiency, and mutation counts were expected to follow baseline mutation rates. Our second model assumed fully penetrant haploinsufficiency…
Publication: Nature, 2017 - nature.com
De novo missense substitutions in the gene encoding CDK8, a regulator of the mediator complex, cause a syndromic developmental disorder
… Parent-child trio-based WGS of a proband with metopic synostosis and ID (subject 3 in … : haploinsufficiency, gain of function, and dominant-negative activity.When haploinsufficiency …
Publication: E Calpena, A Hervieu, T Kaserer… - The American Journal of …, 2019 - cell.com
A track record on SHOX: from basic research to complex models and therapy
… Consequently, short stature phenotypes were considered to arise as a result of haploinsufficiency of the critical short stature gene in PAR1 (12, 14, 15). Deletion mapping of short stature …
Publication: A Marchini, T Ogata, GA Rappold - Endocrine Reviews, 2016 - academic.oup.com
Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants
… This further supports the candidacy of these genes as novel NDD genes and suggests that haploinsufficiency of these genes is the relevant pathomechanism (Additional file 2: Table S9)…
Publication: K Hamanaka, N Miyake, T Mizuguchi, S Miyatake… - Genome Medicine, 2022 - Springer
Genetic and functional characterization of cerebellar and brainstem congenital defects
… A detailed clinical and neuroradiological assessment of patients and parents showed that SUFU haploinsufficiency gives rise to a neurodevelopmental spectrum ranging from clinically …
Publication: V Serpieri - 2021 - iris.unipv.it
In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular …
… nor haploinsufficiency at this level (Figure 1D). Characterizing conditional Csnk2a1 knockout … analyze whether a similar phenotype is detectable in conditional Csnk2a1 knockout mice (…
Publication: M Merholz, Y Jian, J Wimberg, L Gessler… - Cells, 2022 - mdpi.com
Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway
… Our data show that SETD1A haploinsufficiency results in morphologically increased … This network phenotype is primarily driven by SETD1A haploinsufficiency in glutamatergic neurons. …
Publication: S Wang, JR van Rhijn, I Akkouh, N Kogo, N Maas… - Cell reports, 2022 - cell.com
Response to Reviewer reports
… We further explored the CNV/phenotype correlation and … mutations only in SNRPB and CSNK2A1 have been reported to … supporting their pathogenicity in haploinsufficiency. In case 30, …
Publication: C Xu, Y Xiang, X Xu, L Zhou, H Li, X Dong, S Tang - assets.researchsquare.com
De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features
… Prenatal histories were largely unremarkable except for polyhydramnios in one patient. … of action for the CSNK2A1 variants we report, but there are predicted loss-of-function alleles in …
Publication: V Okur, MT Cho, L Henderson, K Retterer, M Schneider… - Human genetics, 2016 - Springer
CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy
… -old female patient with ID, hypotonia, and sleep problems. Similarly to our cases, the splice site variant suggests that loss-of-function could be the mechanism of action for CSNK2A1 …
Publication: K Poirier, L Hubert, G Viot, M Rio, P Billuart… - Human …, 2017 - Wiley Online Library
Predictive functional, statistical and structural analysis of CSNK2A1 and CSNK2B variants linked to neurodevelopmental diseases
… All the mutation analyzed in CK2α and CK2β in this study appear in the patient populations … and CK2β are typically deemed as de facto loss-of-function. Determining the impact of these …
Publication: P Unni, J Friend, J Weinberg, V Okur… - Frontiers in Molecular …, 2022 - frontiersin.org
Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations
… Based on the way of affecting protein function, we classified the variants into two categories: loss-of-function (LOF, including start loss, frameshift insertion/deletion, nonsense, and …
Publication: W Zhang, F Ye, S Chen, J Peng, N Pang… - Frontiers in …, 2022 - frontiersin.org
Two different presentations of de novo variants of CSNK2B: two case reports
… and caused variants that lead to loss of function [2]. … The patient displayed very similar features to patient #2, including large … Collectively, these cases corroborate the loss of function as …
Publication: MVMB Wilke, BM Oliveira, A Pereira… - Journal of Medical Case …, 2022 - Springer
Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation
… We did not use any AEDs in this case, and the patient had no seizures during the follow-up … Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-a …
Publication: S Yang, L Wu, H Liao, X Lu, X Zhang, X Kuang, L Yang - neurogenetics, 2021 - Springer
Exome sequencing in 16 patients with pituitary stalk interruption syndrome: A monocentric study
… to a CSNK2A1 missense variant. … patient carries a novel loss-of-function nonsense variant, it is possible that this case represents a very mild expression of the PITX2 phenotype. Patient …
Publication: R Brauner, J Bignon-Topalovic, A Bashamboo… - Plos one, 2023 - journals.plos.org
Expanding phenotype of poirier–bienvenu syndrome: new evidence from an italian multicentrical cohort of patients
… CSNK2B, CSNK2A1 and CSNK2A2 which is involved in several signaling pathways [5,9]. … loss of function, occurring in 66% to 100% of patients [1,3,6,14]. In our cohort, only patient 5 …
Publication: A Orsini, A Santangelo, F Bravin, A Bonuccelli… - Genes, 2022 - mdpi.com
Dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in one Chinese patient: a case report
… This is a loss of function variant (PVS1), which is absent in general population (PM2). The patient’s … Our patient has inherited two variants of the CSNK2A1 gene and the TRPS1 gene …
Publication: S Xu, Q Lian, J Wu, L Li, J Song - BMC Medical Genetics, 2020 - Springer
Characterizing CSNK2A1 Mutant-Induced Morphological Phenotypes in Zebrafish (Danio rerio): Insights into Okur-Chung Neurodevelopmental Syndrome (OCNDS)
… However, we also reasoned that this could be applicable to loss-of-function … CSNK2A1 throughout zebrafish development and the rapid integration of the newly synthesized CSNK2A1 …
Publication: K Hassett, SS Potu, A Sankaramoorthy, K Leka… - bioRxiv, 2024 - biorxiv.org
Okur‐Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion
… In brief, genomic DNA was obtained from peripheral blood of the proband-parent trios with QIAamp … We thus postulate loss-of-function as a possible mechanism underlying CSNK2A1 …
Publication: ATG Chiu, SLC Pei, CCY Mak, GKC Leung… - Clinical …, 2018 - Wiley Online Library
Okur-Chung Neurodevelopmental Syndrome Synonym: CSNK2A1-Related Neurodevelopmental Syndrome
… circles are missense pathogenic variants and red-filled circles are loss-of-function (more...) … to be low as the proband most likely has a de novo CSNK2A1 pathogenic variant. There is, …
Publication: ID An - europepmc.org
Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
… complete loss-of-function, high-unstable variants in F1 and F2/3. Interestingly, the proband … The proband in F5 did not show any calcifications on CT at the age of 12 years. The clinical …
Publication: V Chelban, H Aksnes, R Maroofian… - Nature …, 2024 - nature.com
A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms
… For our proband, oral treatment with topiramate was able to … A loss-of-function (lof) mechanism for CDK19 is controversial… the patients results from a simple loss of function of CDK19, but …
Publication: S Yang, W Yu, Q Chen, X Wang - Molecular Case …, 2021 - molecularcasestudies.cshlp.org
Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism
… and the full-scale IQ is shown below each proband. B Sequence analysis of each of the three … To test for enrichment of coding DNVs that were loss-of-function or missense, we applied …
Publication: EM Padhi, TJ Hayeck, Z Cheng, S Chatterjee… - Human genomics, 2021 - Springer
Phosphofurin Acidic Cluster Sorting Protein 1 Syndrome: Insights Gained on the Multisystem Involvement Reviewing Encoded Protein Interactions?
… CSNK2A1 is a subunit of CK2 and CK2-activated … effect on loss of function caused by deletion in the PACS1 gene.[9] … issues were not reported in the proband and this can be therefore …
Publication: S Thakur, P Paliwal, R Farmania… - Journal of Pediatric …, 2022 - thieme-connect.com
Okur-Chung Neurodevelopmental Syndrome
… CSNK2A1 protein (x-axis). Blue-filled circles are missense pathogenic variants and red-filled circles are loss-of-function … proband depends on the genetic status of the proband's parents: …
Publication: W Chung, V Okur - GeneReviews®[Internet], 2022 - ncbi.nlm.nih.gov
Copy number variation in hereditary non-polyposis colorectal cancer
… Loss of function of any one of these genes results in a failure to repair DNA errors occurring … All patients had been diagnosed with CRC and were the first individual (proband) of their …
Publication: AL Masson, BA Talseth-Palmer, TJ Evans, DM Grice… - Genes, 2013 - mdpi.com
Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans
… aberrant LD formation as a cellular phenotype common … Thus, the aberrant LD phenotype is seen in multiple genotypes … In this study, we report that loss-of-function mutations in …
Publication: RP Liegel, MT Handley, A Ronchetti, S Brown… - The American Journal of …, 2013 - cell.com