Acute myeloid leukemia in Baraitser–Winter cerebrofrontofacial syndrome

Cianci, Paola; Fazio, Grazia; Casagranda, Sara; Spinelli, Marco; Rizzari, Carmelo; Cazzaniga, Giovanni; Selicorni, Angelo

doi:10.1002/ajmg.a.38057

Cited by 13 publications

(5 citation statements)

References 18 publications

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“…These patients showed a clinical phenotype compatible with the syndrome diagnosed. In five of these syndromes (Baraitser-Winter syndrome, Coffin-Siris syndrome, Rubinstein-Taybi syndrome, Weaver syndrome and APOB-based hypobetalipoproteinemia), malignancies have been described before (22,23,(34)(35)(36)(37), and the genes involved are also affected by somatic mutations in several cancer types (38)(39)(40). This suggests a role of these mutations in cancer development in these patients, but more studies are needed to firmly establish this relationship.…”

Section: Discussionmentioning

confidence: 99%

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Diets

Waanders

Ligtenberg

et al. 2018

Clinical Cancer Research

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In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome. Four patients carried causative mutations in a known cancer-predisposing gene: and ( = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (-based Rubinstein-Taybi syndrome, -based Coffin-Siris syndrome,-based Baraitser-Winter syndrome, and -based Weaver syndrome). In addition, we identified two genes, and , which are possibly involved in genetic cancer predisposition. In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. .

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Section: Discussionmentioning

confidence: 99%

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Diets

Waanders

Ligtenberg

et al. 2018

Clinical Cancer Research

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“…presenting clinical variability with a high degree of brain malformation (83%, Figure 1C;REF NDD (Verloes et al 2015;Cianci et al 2017). Non-BWCFF variant p.R147S is a hotspot postzygotic ACTB mutations leading to mosaic skin disorders known as Becker nevus syndrome (Cai et al 2017), possibly this variant might be lethal as a homozygous (Happle 2017); while p.R183W is associated with dystonia deafness (Eggink et al 2017;Conboy et al 2017;Gearing et al 2002;Procaccio et al 2006;Zech et al 2017;Skogseid et al 2018;Freitas et al 2019).…”

Section: Resultsmentioning

confidence: 99%

Classification of human actin pathological variants usingC. elegansCRISPR-generated models

Hecquet,

Arbogast,

Suhner

et al. 2024

Preprint

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Actin plays a crucial role in diverse physiological processes via the formation of dynamic networks that determine cellular shape and mechanical properties.De novovariants in cytoskeletal β- and γ-actin, encoded by humanACTBandACTG1genes, lead to a wide range of rare diseases, termed Non-Muscle Actinopathies (NMA). Variants include missense, frameshift, truncating variants up to whole gene deletions and induce diverse symptoms. So far, the high clinical variability and genotype-phenotype correlations in NMA remain largely unresolved. To address this question, we used CRISPR to insert in theC. eleganshomologueact-2gene ninede novomutations identified in patients. Using these animal models, we performed a quantitative multiscale characterisation. We uncovered a variety of perturbations: actin network defects at the micro scale, cell scale abnormalities, morphogenesis failure, as well as weaker behavioural phenotypes. Importantly, the range of developmental defects observed correlates with the severity of patients' symptoms. Thus, we provide evidence that aC. elegans-based approach represents a new way to investigate the mechanisms underlying NMA physiopathology or ultimately screen for therapeutic strategies.

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“…Abbreviations: ALL = acute lymphoblastic leukemia 3 . In addition, a third patient with ACTB-based Baraitser-Winter syndrome who developed AML was identified recently 4 . ACTB is deregulated in multiple malignancies, amongst which also leukemia and lymphoma 5 .…”

Section: Supplementary Tablementioning

confidence: 99%

Supplementary Appendix 1 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Diets¹,

Waanders²,

Ligtenberg³

et al. 2023

Preprint

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<p>Supplementary Table S1 - Cancer gene panel Supplementary Table S2 - Patients with multiple malignancies Supplementary Table S3 - Tumor types of index patients Supplementary Table S4 - Candidate genes Supplementary Table S5 - Overview of clinical features and mutations found in category 1 (ID and/or congenital anomalies) Supplementary Table S6 - Overview of clinical features and mutations found in category 2 (cancer twice) Supplementary Table S7 - Overview of clinical features and mutations found in category 3 (family history) Supplementary Table S8 - Overview of clinical features and mutations found in category 4 (adult type of cancer) Supplementary Table S9 - Overview of clinical features and mutations found in category 5 (multiple reasons for inclusion) Supplementary Figure S1 - Detection of mosaic mutation in ARID1A Supplementary Figure S2 - Family tree of case #04 Supplementary Figure S3 - Family tree of case #05 Supplementary Figure S4 - Family tree of case #07 Supplementary Figure S5 - Family tree of case #10 Supplementary Figure S6 - Family tree of case #12 Supplementary Figure S7 - Family tree of case #17 Supplementary Figure S8 - Family tree of case #21 Supplementary Figure S9 - Family tree of case #22 Supplementary Figure S10 - Family tree of case #24 Supplementary Figure S11 - Family tree of case #27 Supplementary Figure S12 - Family tree of case #28 Supplementary Figure S13 - Family tree of case #29 Supplementary Figure S14 - Family tree of case #34 Supplementary Figure S15 - Family tree of case #36 Supplementary Figure S16 - Family tree of case #39</p>

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Acute myeloid leukemia in Baraitser–Winter cerebrofrontofacial syndrome

Cited by 13 publications

References 18 publications

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Classification of human actin pathological variants usingC. elegansCRISPR-generated models

Supplementary Appendix 1 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

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