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Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder
… In agreement with the single previously reported patient, these individuals show clinical … disorders showing clinical overlap with KMT2C haploinsufficiency. Promising candidates to be …
Publication: TS Koemans, T Kleefstra, MC Chubak, MH Stone… - PLoS …, 2017 - journals.plos.org
This dataset pertains to a study on the gene KMT2C and its role in neurodevelopmental disorders. Out of the clinical genetics centers at the Radboudumc and Maastricht UMC, five individuals exhibiting symptoms of intellectual disability (ID), language and motor delay, autism or Pervasive Developmental Disorder (PDD) were identified with de novo KMT2C mutations predicted to induce loss of function. These mutations included a frameshift mutation c.5216del (p.Pro1739Leufs*2) in individual 1, a mosaic nonsense mutation c.7550C>G (p.Ser2517*) in approximately 30% of blood cells of individual 2, another nonsense mutation c.1690A>T (p.Lys564*) in individual 3, a frameshift mutation c.10812_10815del (p.Lys3605fs) in individual 4, and a de novo deletion involving an intragenic 203kb segment (Chr7: 151858920–152062163)x1 in individual 5. Inheritance testing confirmed the de novo status of these mutations. Additionally, clinical features recurrent across cases included short stature, microcephaly, childhood hypotonia, kyphosis, scoliosis, recurrent respiratory infections, and Kleefstra-like facial dysmorphisms. Functional studies supported the relationship between KMT2C mutations and the disease phenotype, particularly an intragenic de novo deletion identified by microarray-based comparative genomic hybridization and confirmed by locus-specific qPCR in one patient. These findings collectively support a role of haploinsufficiency in KMT2C contributing to the clinical phenotype of the disease.
Identification of a new mutation in kmt2c causing Kleefstra syndrome TYPE 2: A very rare disorder characterized by autism and development delay
… by haploinsufficiency of … of a patient affected by type 2 Kleefstra syndrome, for which the diagnosis was performed at 3 years old. In addition to typical clinical signs of KLEFS2 our patient …
Publication: A Peduto, MD et PhD, E Barabesi, MC Giraudo… - jmedcasereportsimages.org
This synthesis provides an overview of the case-level genetic evidence for KMT2C haploinsufficiency in human disease. Two cases were analyzed, each with distinct loss-of-function mutations in the KMT2C gene. The first case, a Caucasian child, presented with developmental delay and autism with typical clinical signs of Kleefstra syndrome type 2 (KLEFS2) and orthopedic anomalies; a novel de novo nonsense mutation c.10420C>T (p.Gln3474Ter) was identified, which is believed to impair gene function. The second case, details not provided, exhibited intellectual impairment, autism, and lack of language along with dysmorphic features, with a de novo truncating mutation in the KMT2C gene also detected. Genetic inheritance was tested in both instances, with the mutations arising de novo. Functional studies suggested that truncating mutations in KMT2C were involved in the clinical manifestations, including intellectual impairment and autistic features, and implicated KMT2C in neurodevelopmental disorders such as Kleefstra syndrome type 2, Kabuki, and Rubinstein-Taybi syndromes. Collectively, these findings demonstrate the recurrence of clinical features associated with KMT2C haploinsufficiency, such as developmental delays, limited language abilities, hypotonia, facial dysmorphisms, and varying systemic anomalies, supporting its role in the pathogenesis of related syndromes.
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Haploinsufficiency of KMT2E results in transcriptional changes and leads to non-syndromic intellectual disability
… the patients overgrowth symptoms were due to the haploinsufficiency of KMT2E. We conducted exome sequencing for a cognitively disabled patient, who was presented in Tübingens …
Publication: EU Melchinger - 2022 - ub01.uni-tuebingen.de
KMT2C/D COMPASS complex-associated diseases [KCDCOM-ADs]: an emerging class of congenital regulopathies
… ), and Kleefstra syndrome type 2 (KMT2C). Here, we review the … KMT2C/D COMPASS complex are highlight with a focus on clinically relevant mechanisms sensitive to haploinsufficiency…
Publication: WJ Lavery, A Barski, S Wiley, EK Schorry… - Clinical …, 2020 - Springer
Haploinsufficiency of KMT2B, encoding the lysine-specific histone methyltransferase 2B, results in early-onset generalized dystonia
… Suggestive of haploinsufficiency, we found significantly decreased total mRNA levels of … dystonia as the human phenotype associated with haploinsufficiency of KMT2B. Moreover, we …
Publication: M Zech, S Boesch, EM Maier, I Borggraefe, K Vill… - The American Journal of …, 2016 - cell.com
The developmental logic of enhanceropathies caused by KMT2D and YY1 haploinsufficiency through patient-derived disease modeling platforms
… As with KMT2A and B, KMT2C and KMT2D have a partially redundant role: the deletion of … Mice model for Kmt2c and Kmt2d have phenotype onset remarkably different: Kmt2c depleted …
Publication: M Gabriele - 2019 - air.unimi.it
Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4)
… KMT2D knockout and Kabuki patient-derived cell models to … suggesting KMT2D haploinsufficiency impact bivalent … homozygous knockout of both Kmt2d and Kmt2c in rodents. But …
Publication: M Jefri, X Zhang, PS Stumpf, L Zhang… - Human molecular …, 2022 - academic.oup.com
Two new cases of interstitial 7q35q36.1 deletion including CNTNAP2 and KMT2C
… Importantly, recently de novo mutations of KMT2C gene were … 2, the Decipher patient #303634 carrying a KMT2C intragenic … Thus, KMT2C haploinsufficiency may have strongly …
Publication: L Tosca, L Drévillon, A Mouka, L Lecerf… - Molecular genetics & …, 2021 - Wiley Online Library
KMT2D haploinsufficiency in Kabuki syndrome disrupts neuronal function through transcriptional and chromatin rewiring independent of H3K4-monomethylation
… of KMT2D, to fully mimic its haploinsufficiency. We used patient-derived tissues, and iPSCs and … Remarkably, we found KMT2D to bind its regulatory region and KMT2A, KMT2B, KMT2C, …
Publication: M Gabriele, A Vitriolo, S Cuvertino, MF Pereira… - bioRxiv, 2021 - biorxiv.org
A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia
… Among these, CTLA4 haploinsufficiency has both autoimmunity and immunodeficiency … have had a significant impact on T-cell function, as in the case of CTLA4 haploinsufficiency. …
Publication: S Tamura, H Kosako, Y Furuya, Y Yamashita… - Acta …, 2022 - karger.com
Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder
… In agreement with the single previously reported patient, these individuals show clinical … disorders showing clinical overlap with KMT2C haploinsufficiency. Promising candidates to be …
Publication: TS Koemans, T Kleefstra, MC Chubak, MH Stone… - PLoS …, 2017 - journals.plos.org
P629: A novel 198 kb partial duplication in KMT2C: Report of a patient with features of Kleefstra syndrome-2 and adrenal ganglioneuroblastoma
… by haploinsufficiency of the KMT2C gene. … in KMT2C reported in the literature to date. We present an additional case of a partial duplication disrupting KMT2C found in a pediatric patient …
Publication: R Gaur, J Herriges, I Thiffault, J Joyce, E Rush… - Genetics in Medicine …, 2024 - gimopen.org
COMPASS Ascending: Emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer
… Haploinsufficiency of the human 7q chromosome region in acute myeloid leukemia implicated KMT2C … This dual role of KMT2C in breast cancer cell lines is consistent with patient data, …
Publication: RJ Fagan, AK Dingwall - Cancer letters, 2019 - Elsevier
Modelling Haploinsufficiency of Histone Modifier Genes Using Human Cell Models
… Lysine-specific methyltransferase 2B KMT2C … • I found KMT2D haploinsufficiency causes an up-regulation of genes … in neurodevelopmental disorders caused by haploinsufficiency of an …
Publication: M Jefri - 2022 - search.proquest.com
Precise definition of the breakpoints of an apparently balanced translocation between chromosome 3q26 and chromosome 7q36: Role of KMT2C disruption
… disrupted the KMT2C gene, the haploinsufficiency of which leads … this patient and previously reported patient with KMT2C … study, the contribution of KMT2C disruption would never have …
Publication: M Yamada, H Suzuki, F Miya… - Congenital …, 2023 - Wiley Online Library
Identification of a new mutation in kmt2c causing Kleefstra syndrome TYPE 2: A very rare disorder characterized by autism and development delay
… by haploinsufficiency of … of a patient affected by type 2 Kleefstra syndrome, for which the diagnosis was performed at 3 years old. In addition to typical clinical signs of KLEFS2 our patient …
Publication: A Peduto, MD et PhD, E Barabesi, MC Giraudo… - jmedcasereportsimages.org
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia
… oromandibular features (patient 18) or paroxysmal cervical dystonia (patient 26a) and … interstitial microdeletions leading to KMT2B haploinsufficiency or variants predicted to cause …
Publication: E Meyer, KJ Carss, J Rankin, JME Nichols, D Grozeva… - Nature …, 2017 - nature.com
SNP-array lesions in core binding factor acute myeloid leukemia
… [19], was seen in one patient as the sole secondary abnormality. … that KMT2C act as a tumor suppressor gene in AML [16]. Together, these data suggest that KMT2C haploinsufficiency is …
Publication: N Duployez, E Boudry-Labis, C Roumier, N Boissel… - Oncotarget, 2018 - ncbi.nlm.nih.gov
Aberrant activity of histone–lysine n-methyltransferase 2 (Kmt2) complexes in oncogenesis
… suppressor, resulting in poor patient survival in many types … on KMT2C/KMT2D and PTIP and correlated with KMT2C/KMT2D… to tumorigenesis and that haploinsufficiency alone does not …
Publication: E Poreba, K Lesniewicz, J Durzynska - International journal of molecular …, 2020 - mdpi.com
Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile
… ” associated with KMT2B haploinsufficiency, proving that this … Different from the other members of the KMT2 family, KMT2C … rejected a diagnosis of DYT28 in patient 18, who carried the p.…
Publication: A Ciolfi, A Foroutan, A Capuano, L Pedace… - Clinical …, 2021 - Springer
Alternative transcripts in variant interpretation: the potential for missed diagnoses and misdiagnoses
… 55 of KMT2C (NM_170606.3) was reported. KMT2C haploinsufficiency causes Kleefstra … only one had—this was a female patient with a frameshift variant with clinical features including …
Publication: K Schoch, QKG Tan, N Stong, KL Deak… - Genetics in …, 2020 - nature.com
Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome
… syndrome associated with haploinsufficiency of SETD1A by … We examined cellular phenotypes in three patient-derived … that we describe in SETD1A haploinsufficiency, as the cognitive …
Publication: J Kummeling, DE Stremmelaar, N Raun… - Molecular …, 2021 - nature.com
A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2
… in the KMT2C gene, not previously reported in the literature. The affected proband has two older … by which early termination and NMD result in haploinsufficiency of the KMT2C protein. …
Publication: W Whitford, J Taylor, I Hayes, W Smith… - … Genetics & Genomic …, 2024 - Wiley Online Library
Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
… Kleefstra syndrome 2 is a rare condition caused by variants in KMT2C with moderate to … other histone lysine methyltransferases and demethylases (KMT2C, SETD1A (KMT2F), KDM6A …
Publication: LM Reis, H Atilla, P Kannu, A Schneider, S Thompson… - Genes, 2023 - mdpi.com
Histone lysine methylases and demethylases in the landscape of human developmental disorders
… KMT2C, ASH1L, and KMT5B haploinsufficiency with dominant developmental disorders. Whereas KMT2C or ASH1L haploinsufficiency … who did not share the proband’s phenotype. …
Publication: V Faundes, WG Newman, L Bernardini… - The American Journal of …, 2018 - cell.com
Bi-Allelic Pathogenic Variants in KMT2C Cause Oocyte Maturation Arrest in Women and Mice
… KMT2C exhibits high expression in the brain, and the presence of heterozygous 115 protein-truncating variants in KMT2C suggests that haploinsufficiency primarily leads 116 …
Publication: P Yuan, T Jiang, Q Liao, P Cong, Y Li, H Zhao… - Available at SSRN … - papers.ssrn.com
Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanese family with minor malformations, intellectual disability, and …
… In the proband, we estimated her systemic score was at least … by haploinsufficiency or suspected haploinsufficiency of … are caused by haploinsufficiency of the KMT2D and KMT2C, …
Publication: S Yokotsuka-Ishida, M Nakamura, Y Tomiyasu… - Journal of Human …, 2021 - nature.com
Identification of clinically actionable variants from genome sequencing of families with congenital heart disease
… An HNRNPK Ser420Leu variant was found in proband 1746 with ASD. Variants resulting in haploinsufficiency … Two KMT2C frameshift insertions were found in probands 939 and 3595. …
Publication: D Alankarage, E Ip, JO Szot, J Munro, GM Blue… - Genetics in …, 2019 - Elsevier
Kleefstra syndrome
… The diagnosis of MBD5 haploinsufficiency is established in a proband with one of the following: deletion of 2q23.1 that encompasses all or part of MBD5 (~90% of affected individuals); …
Publication: T Kleefstra, N de Leeuw - 2019 - europepmc.org
P630: Multi-modal testing, including long-read sequencing, to elucidate an unsolved case of dyskeratosis congenita
… duplication involving KMT2C is 198 kb in size, with two … of a partial duplication in KMT2C. Patient’s developmental … ” haplotype was present in the proband. Subsequent telomere length …
Publication: A Jhuraney, S Paolucci, S Gibson… - Genetics in Medicine …, 2024 - gimopen.org
Exome sequencing identifies three novel candidate genes implicated in intellectual disability
… sequencing was performed for the proband of each family. The … with KS was caused by haploinsufficiency of EHMT1, while … the single ortholog of mammalian KMT2C and KMT2B, and …
Publication: Z Agha, Z Iqbal, M Azam, H Ayub, LELM Vissers… - PloS one, 2014 - journals.plos.org
Postzygotic and germinal de novo mutations in ASD: exploring their biological role
… KMT2C have been detected in individuals affected by Kleefstra syndrome 2 (OMIM #617768). Kleefstra syndrome is caused by haploinsufficiency … the detection of KMT2C association in …
Publication: A Alonso-González, M Calaza, J Amigo… - bioRxiv, 2020 - biorxiv.org
Kleefstra Syndrome Synonyms: 9q34. 3 Microdeletion Syndrome, 9qSTDS, 9q Subtelomeric Deletion Syndrome
… The diagnosis of MBD5 haploinsufficiency is established in a proband with one of the following: deletion of 2q23.1 that encompasses all or part of MBD5 (~90% of affected individuals); …
Publication: T Kleefstra, N de Leeuw - europepmc.org
Refining the phenotypic spectrum of KMT5B-associated developmental delay
… Proband A presented at 12 months of age due to global … as well as its highly homologous counterpart KMT2C, is a lysine … this subgroup of patients is haploinsufficiency. In contrast, three …
Publication: A Eliyahu, O Barel, L Greenbaum, G Zaks Hoffer… - Frontiers in …, 2022 - frontiersin.org
Atypical cerebral palsy: genomics analysis enables precision medicine
… families only the proband (n = 4) or the proband and one … explained by homozygous variants in KMT2C. This is likely an … A model other than haploinsufficiency may have to be involved …
Publication: AM Matthews, I Blydt-Hansen, B Al-Jabri, J Andersen… - Genetics in …, 2019 - Elsevier
Michael Zech, Sylvia Boesch, 3 Esther M. Maier, 4 Ingo Borggraefe, 4 Katharina Vill, 4 Franco Laccone, 5 Veronika Pilshofer, 6 Andres Ceballos-Baumann, 2, 7 …
… Suggestive of haploinsufficiency, we found significantly … the initial proband-only exome approach by performing full … ioral difficulties; mutations in KMT2C have been linked to Kleefstra …
Publication: TB Haack, B Haslinger, TM Strom, J Winkelmann - 2016 - academia.edu
Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy
… Family pedigree of the proband (black arrow), in whom we detected a de novo c.2028delT (P677LfsX19) mutation in SETD2 (red arrows on electropherogram) (Color figure online) …
Publication: HS Lumish, J Wynn, O Devinsky, WK Chung - Journal of autism and …, 2015 - Springer
Characterizing Genomic Duplication in Autism Spectrum Disorder
… Haploinsufficiency is the predominant disease mechanism associated with known ASD risk … haploinsufficiency. Interpreting the significance of partial and whole gene duplications at …
Publication: EJ Higginbotham - 2020 - search.proquest.com
Loss of KMT2C, A Subunit of the Compass-Like Complex, Cooperates with Oncogenic Signaling in Cancer
… of patient data and the aforementioned study of Kmt2c haploinsufficiency, I tested the hypothesis that Kmt2c functions as a haploinsufficient tumor suppressor in MEFs, and …
Publication: G Prado - 2022 - search.proquest.com
KMT2A: Umbrella Gene for Multiple Diseases
… ; CdLS5, OMIM #300882)-like phenotype were found carriers of pathogenetic variants in … in six patients with an RSTS-like phenotype but negative for RSTS known causative genes, …
Publication: S Castiglioni, E Di Fede, C Bernardelli, A Lettieri… - Genes, 2022 - mdpi.com
KMT2A‐D pathogenicity, prevalence, and variation according to a population database
… have supported somatic KMT2C haploinsufficiency in acute … of germline missense variants in KMT2C, found complete loss … variants contribute to the phenotype of certain conditions. …
Publication: JK Larson, DVN Hunter‐Schlichting… - Cancer …, 2023 - Wiley Online Library
Clinical Characteristics and Genotype–Phenotype Correlation in Children with KMT2E Gene-Related Neurodevelopmental Disorders: Report of Two New Cases and …
… The previous authors hypothesized haploinsufficiency as the most plausible pathogenetic … [10] The more severe phenotype in individuals with 7q22.2–22.3 microdeletions might be …
Publication: IK Sharawat, PK Panda, L Dawman - Neuropediatrics, 2021 - thieme-connect.com
Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1
… and the resulting KS1 phenotype, meaning that a given variant may not lead to the same features in all patients. Mosaicism of KMT2D variants further complicate the KS1 phenotype by …
Publication: CS Golden, S Williams, MA Serrano - Birth defects research, 2023 - Wiley Online Library
Association of KMT2C/D loss‐of‐function variants with response to immune checkpoint blockades in colorectal cancer
… in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/… investigated the associations of KMT2C/D loss‐of‐function (LOF) …
Publication: R Liu, Y Niu, C Liu, X Zhang, J Zhang, M Shi… - Cancer …, 2023 - Wiley Online Library
Recruitment of KMT2C/MLL3 to DNA damage sites mediates DNA damage responses and regulates PARP inhibitor sensitivity in cancer
… loss-of-function. No hotspot mutations were observed, although mutations seemed clustered in the N-terminus of KMT2C … mutations of each gene in each patient. Bar plots (right) show …
Publication: A Chang, L Liu, JM Ashby, D Wu, Y Chen, SS O'Neill… - Cancer research, 2021 - AACR
KMT2C Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition
… methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient tumors. … lead to the defect of substrate recognition, and thus loss of function of KMT2C methyltransferase. …
Publication: SJ Cho, C Yoon, JH Lee, KK Chang, J Lin, YH Kim… - Clinical Cancer …, 2018 - AACR
KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors
… We found that both KMT2A (P = 0.007) and KMT2C (P = 0.041… Then we combined KMT2A and KMT2C mutation as KMT2A/… /C mutations can cause loss of function in the proteins, which …
Publication: R Zhang, HX Wu, M Xu, X Xie - Biomarker Research, 2020 - Springer
Analysis of the role of mutations in the KMT 2D histone lysine methyltransferase in bladder cancer
… in papillary tumors and loss-of-function mutations in tumor … KMT2D, KMT2C, and KMT2A were most frequently mutated … , mRNA expression, and overall patient survival in 426 samples. …
Publication: B Ding, L Yan, Y Zhang, Z Wang, Y Zhang… - FEBS open …, 2019 - Wiley Online Library
Loss of Kmt2c in vivo leads to EMT, mitochondrial dysfunction and improved response to lapatinib in breast cancer
… sequencing analysis on breast cancer patient samples to reveal the … Kmt2c loss of function mutations. A possible explanation of this finding could be that the genetic ablation of Kmt2c …
Publication: N Simigdala, A Chalari, AD Sklirou… - Cellular and Molecular …, 2023 - Springer
KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis
… KMT2C mutations (7%), suggestive of a crucial role in carcinogenesis [15]. A substantial number of mutations detected in KMT2C lead to loss of function … in the KMT2C truncated patient …
Publication: T Limberger, M Schlederer, K Trachtová… - Molecular Cancer, 2022 - Springer
Clinicopathologic and genetic features of primary T-cell lymphomas of the central nervous system: an analysis of 11 cases using targeted gene sequencing
… case had a frameshift mutation in KMT2C, another PTCL-NOS … sequencing using the patient’s peripheral blood sample. The … Loss-of-function mutations of BCOR have been reported in …
Publication: J Yim, J Koh, S Kim, SG Song, JM Bae… - The American Journal …, 2022 - journals.lww.com
Large-scale analysis of KMT2 mutations defines a distinctive molecular subset with treatment implication in gastric cancer
… with KMT2C wild-type (WT) [14]. Mechanically, loss-of-function mutations of KMT2C may … Therefore, this study is considered IRB exempt and no patient consent was necessary from …
Publication: J Wang, J Xiu, Y Baca, F Battaglin, H Arai, N Kawanishi… - Oncogene, 2021 - nature.com
Loss of function of the gene encoding the histone methyltransferase KMT2D leads to deregulation of mitochondrial respiration
… Using RNA-Seq analysis, it was revealed that KMT2D is, along with KMT2C, a key epigenetic … The mutations in KMT2D carried on by each Kabuki patient are indicated in (A). (A) and (B) …
Publication: C Pacelli, I Adipietro, N Malerba, GM Squeo, C Piccoli… - Cells, 2020 - mdpi.com
Analysis of mutational profile of hypopharyngeal and laryngeal head and neck squamous cell carcinomas identifies KMT2C as a potential tumor suppressor
… a KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrated that KMT2C loss-of-function … cancer cell lines, our patient-based data is supported by …
Publication: MM Machnicki, A Rzepakowska, JI Janowska… - Frontiers in …, 2022 - frontiersin.org
Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Cancers Identifies KMT2C as a Potential Tumor Suppressor
… KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrate that KMT2C loss-of-function results … cancer cell lines, our patient-based data is supported by …
Publication: MM Machnicki, A Rzepakowska, JI Janowska, M Pepek… - medRxiv, 2021 - medrxiv.org
Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients
… of KMT2C mutations in different patient subgroups. Lastly, we investigated the predictive value of KMT2C … Thus its loss of function may confer sensitivity to poly (ADP-ribose) polymerase …
Publication: S Zhu, N Xu, J Liang, F Zhao, Z Wang, Y Ni… - Oncology …, 2023 - ncbi.nlm.nih.gov
KMT2C mediates the estrogen dependence of breast cancer through regulation of ERα enhancer function
… loss of function but given that over 55% of KMT2C mutations are truncation mutations and given the lack of a specific hotspot mutation, our KMT2C … of KMT2C impacted patient survival. …
Publication: K Gala, Q Li, A Sinha, P Razavi, M Dorso… - Oncogene, 2018 - nature.com
Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors
… Consistent with its loss-of-function mutations, KMT2D can act as a tumor suppressor (Table 1). We have shown that brain-specific loss of Kmt2d alone induces spontaneous …
Publication: SS Dhar, MG Lee - Oncotarget, 2021 - ncbi.nlm.nih.gov
Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants
… De novo loss-of-function (LoF) variants in the KMT2A gene … In both patients where the proband had a diagnosis of ADHD, … gene similar to ARID1B and KMT2C. De novo LoF and …
Publication: AJS Chan, C Cytrynbaum, N Hoang… - NPJ Genomic …, 2019 - nature.com
Ehmt2 Loss-of-function Alterations Cause a Kleefstra-like Syndrome
… In addition, loss-of-function mutations in the KMT2C (MLL3) gene … Proband ND095 was remitted to the undiagnosed rare … The proband is a male that suffered from intrauterine growth …
Publication: M Barrero, B Martínez-Delgado, E López-Martín… - 2024 - researchsquare.com
Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations
… with a BD proband (56 with … KMT2C, MACF1 and UNC13B are hit by a de novo LOF mutation despite their extremely high intolerance to protein-altering variants 38 (Table 1). KMT2C (…
Publication: M Kataoka, N Matoba, T Sawada, AA Kazuno… - Molecular …, 2016 - nature.com
Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders
… Parent-proband trio studies have sought to increase power by … Loss-of-function variants in at least five other genes in this … and copy number variants in KMT2C, KMT2E, KDM5B and …
Publication: T Singh, MI Kurki, D Curtis, SM Purcell, L Crooks… - Nature …, 2016 - nature.com
Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene
… due to lack of reads supporting the indel in the proband or existence of multiple reads supporting the indel in either … The de novo frameshift indel (D424fs) in the first proband creates an …
Publication: A Takata, B Xu, I Ionita-Laza, JL Roos, JA Gogos… - Neuron, 2014 - cell.com
EHMT2 LOSS-OF-FUNCTION ALTERATIONS CAUSE A KLEEFSTRA-LIKE SYNDROME
… In addition, loss-of-function mutations in the KMT2C (MLL3) gene cause a … Proband ND095 was remitted to the undiagnosed rare … The proband suffered from global developmental delay …
Publication: B Martinez-Delgado, E Lopez-Martin, J Kerkhof… - medRxiv, 2024 - medrxiv.org
Systematic analysis of exonic germline and postzygotic de novo mutations in bipolar disorder
… we find significant enrichment of loss-of-function mutations in … Consistent with our results indicating association of KMT2C … , in the case of BD proband with an LoF variant in KMT2C, the …
Publication: M Nishioka, A Kazuno, T Nakamura, N Sakai… - Nature …, 2021 - nature.com
Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy
… In our cohort, germline variants were found to disrupt RUNX1 mainly in following 2 ways: (1) loss-of-function variants truncating or completely deleting the RUNX1 protein and (2) …
Publication: K Yu, N Deuitch, M Merguerian, L Cunningham… - Blood …, 2024 - ashpublications.org
A novel neurodevelopmental syndrome caused by loss-of-function of the Zinc Finger Homeobox 3 (ZFHX3) gene
… Here, we identify loss-of-function variation in ZFHX3 as a novel … Loss-of-function variation of ZFHX3 consistently associates … In conclusion, loss-of-function variants in ZFHX3 are a novel …
Publication: MR Pérez Baca, E Jacobs, L Vantomme… - Joint BeSHG/NVHG …, 2022 - biblio.ugent.be
De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis
… Analysis of exome sequence data from 526 proband-parent trios with syndromic CS … À20 ) of damaging de novo variants (DNVs) in genes highly intolerant to loss-of-function variation (…
Publication: AT Timberlake, S McGee, G Allington, E Kiziltug… - The American Journal of …, 2023 - cell.com
Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants
… site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, … , proband MC-17-3 presented with epilepsy, the characteristic phenotype in patients with SCN1A loss of function …
Publication: IO Tuncay, NL Parmalee, R Khalil, K Kaur… - NPJ Genomic …, 2022 - nature.com
A clustering of heterozygous missense variants in the crucial chromatin modifier WDR5 defines a new neurodevelopmental disorder
… (Thr208Met)) in WDR5 in a proband with childhood apraxia … for both missense and lossof-function variation. The gene has a … but has no visible interactions with the KMT2C protein. …
Publication: LS Blok, J Verseput, D Rots, H Venselaar… - Human Genetics and …, 2023 - cell.com
Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression
… loss-of-function effect [25, 26] motivated us to examine the role of KMT2C in CRC cells by restoring wild type KMT2C in … The altered growth phenotype of RKO KMT2C insG clones was …
Publication: C Larsson, L Cordeddu, L Siggens, T Pandzic… - Clinical …, 2020 - Springer
The lysine‐specific methyltransferase KMT 2C/MLL 3 regulates DNA repair components in cancer
… and SCR7 ameliorated this phenotype. Comparable results were … KMT2C is significantly downregulated in many different types of cancer. We thus speculate that loss‐of‐function …
Publication: T Rampias, D Karagiannis, M Avgeris, A Polyzos… - EMBO …, 2019 - embopress.org
KMT2C, a histone methyltransferase, is mutated in a family segregating non-syndromic primary failure of tooth eruption
… We consider KMT2C as a strong candidate gene for PFE phenotype based on the role of another member of histone methyltransferase (KMT2D) in tooth development and highly similar …
Publication: AA Assiry, AM Albalawi, MS Zafar, SD Khan, A Ullah… - Scientific Reports, 2019 - nature.com
Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction
… Loss-of-function mutations in the KMT2 family of genes are implicated in various chromatinopathies, including Kleefstra Syndrome type-2 (KLEFS-2) and Kabuki Syndrome type-1 …
Publication: SD Jorge, YI Chi, JL Mazaba, N Haque… - Frontiers in …, 2023 - frontiersin.org
KMT2C and KMT2D aberrations in breast cancer
… -type level predict a loss-of-function (LOF) mode of action for KMT2C in breast cancer, although … The role of Kmt2c loss in this phenotype is supported by a significant reduction in global …
Publication: E Tinsley, P Bredin, S Toomey, BT Hennessy… - Trends in Cancer, 2024 - cell.com
Deciphering brain metastasis stem cell properties from colorectal cancer highlights specific stemness signature and shared molecular features
… cell lines and tumor samples presented an MSS phenotype. … tumor suppressor protein with a loss of function. It is very interesting … Recently, KMT2C loss of function mutations is positively …
Publication: A Desette, PO Guichet, S Emambux… - Cellular and Molecular …, 2023 - Elsevier