Gorlin-like phenotype in a patient with a PTCH2 variant of uncertain significance

Casano, Kelsey; Meddaugh, Hannah; Zambrano, Regina; Marble, Michael; Torres, Jairo I.; Lacassie, Yves

doi:10.1016/j.ejmg.2020.103842

Cited by 13 publications

(11 citation statements)

References 19 publications

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“… 21 Mutation loads < 5%, which could conceivably be present in cases with postzygotic mosaicism (in PTCH1 or SMO ), are impossible to detect using Sanger sequencing. 11 , 12 , 26 Mutations in the PTCH2 gene have also been reported, 10 , 27 , 28 but probably have an insignificant contribution to the cause of BCNS. 29 If a variation is found, the relevance of the mutation and its consequences for the protein function should be verified according to the standards and guidelines set forward by (inter)national organizations.…”

Section: Summary Of Recommendationsmentioning

confidence: 99%

A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome)*

et al. 2021

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The overall objective of this guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and surveillance of all symptoms in children and adults with either basal cell naevus syndrome (BCNS), a clinical suspicion of BCNS, or a parent with BCNS. In the last two groups, the guidelines should be followed until the diagnosis of BCNS can be rejected with certainty. The guideline aims to:• Update and expand on the previous guidelines by an appraisal of all relevant literature from January 2011 up to January 2021• Address important, practical, clinical questions relating to the primary guideline objective• Provide guideline recommendations • Discuss potential developments and future directions The guideline is presented as a detailed review with highlighted recommendations for practical use in the clinic by dermatologists and other healthcare professionals, including general practitioners, clinical geneticists, paediatricians, ophthalmologists, craniomaxillofacial surgeons, neurologists, cardiologists and psychologists. ExclusionsThe guideline does not cover therapeutic recommendations for (nondermatological) symptoms, as the guideline mainly focuses on screening and follow-up of symptoms. Therapeutic recommendations for basal cell carcinomas (BCCs) in general have been published in international BCC guidelines. 1,2 Stakeholder involvement and peer reviewThe guideline was developed at the Maastricht University Medical Centre (MUMC+), the Dutch BCNS expert centre accredited

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Section: Summary Of Recommendationsmentioning

confidence: 99%

A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome)*

et al. 2021

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“…NBCCS is caused by germline heterozygous pathogenic variants in PTCH1 or SUFU . Pathogenic variants in PTCH2 have been identified in a few patients with a mild phenotype of NBCCS [33]. Microdeletions involving 9q22.3, which encompasses PTCH1 , cause overlapping but more severe phenotypes or additional findings, such as overgrowth and Wilms tumor [34].…”

Section: Methodsmentioning

confidence: 99%

Tumor predisposition: what's the skin got to do with it?

Stacy

Shinawi

Coughlin

2022

Current Opinion in Pediatrics

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Purpose of reviewRecognition of skin findings associated with tumor predisposition syndromes can prompt early evaluation and surveillance and improve management. Additionally, knowing when to test and when to defer performing genetic testing can streamline management. This article reviews tumor predisposition syndromes with recently characterized skin findings and disorders for which early recognition and counseling can impact the course of disease.Recent findingsCafé au lait macules (CALMs) are important in many tumor predisposition syndromes, and ‘atypical’ CALMs are associated with constitutional mismatch repair deficiency and Fanconi anemia. Melanoma predisposition syndromes caused by pathogenic variants in POT1 and BAP1 are more recently described, and both are associated with Spitzoid tumors. Somatic pathogenic variants can cause segmental nevoid basal cell carcinoma syndrome and a mosaic form of Peutz–Jeghers syndrome. Patients with PTEN hamartoma syndrome have increased risk for melanoma but this might not occur until adulthood.SummaryThe cutaneous manifestations of tumor predisposition syndromes can aid diagnosis. Early photoprotection is key to modifying a main risk factor for skin cancer in many of these syndromes. Implementing surveillance guidelines facilitates early detection of tumors.

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“…Acute myeloid leukemia (AML) is a life-threatening hematological cancer involving the myeloid cells generated by bone marrow ( 1 ). Furthermore, AML is a genetically heterogeneous clonal disorder, characterized by the accumulation of somatic modifications in hematopoietic progenitor cells that affect their normal self-renewal, proliferation and variation, all of which are involved in hematopoiesis ( 2 ). Hematopoietic stem cells also contribute to hematopoiesis via these processes ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of differentially expressed genes induced by aberrant methylation in acute myeloid leukemia using integrated bioinformatics analyses

et al. 2022

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Acute myeloid leukemia (AML) is a life-threatening hematological malignant disease. Methylation plays a crucial role in the etiology and pathogenesis of AML. The aim of the present study was to identify the aberrantly methylated differentially expressed genes (DEGs) in AML and determine the underlying mechanisms of tumorigenesis by conducting integrated bioinformatics analyses. Gene expression profiles (GSE109179, GSE142699, GSE49665 and GSE14772) and a gene methylation profile (GSE42042) were analyzed to identify the aberrantly methylated DEGs. Functional enrichment analyses of identified genes were conducted based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and protein-protein interaction networks were established. Finally, the DEGs were validated by the reverse transcription-quantitative PCR analysis of patient samples. A total of seven downregulated hypermethylated genes and eight upregulated hypomethylated genes were validated. The differentially methylated DEGs were enriched in GO biological process terms associated with control of the immune response and the KEGG analysis indicated they were involved in AML, ferroptosis, TGF-β signaling and necroptosis pathways. Additionally, five downregulated hypermethylated genes that were also tumor suppressor genes (TSGs) were identified. In vitro assays revealed that the overexpression of transcription factor 7 (TCF7) and integrin a M (ITGAM) significantly inhibited the proliferation of HL60 cells; by contrast, the knockdown of TCF7 and CAMK4 promoted HL60 cell proliferation. Overall, the present study identified differentially methylated DEGs and pathways associated with AML, which may enhance the understanding of the underlying molecular mechanisms of AML. In the future, abnormally methylated oncogenes and TSGs may function as biomarkers and treatment targets for the diagnosis and treatment of AML.

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Gorlin-like phenotype in a patient with a PTCH2 variant of uncertain significance

Cited by 13 publications

References 19 publications

A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome)*

A guideline for the clinical management of basal cell naevus syndrome (Gorlin–Goltz syndrome)*

Tumor predisposition: what's the skin got to do with it?

Identification of differentially expressed genes induced by aberrant methylation in acute myeloid leukemia using integrated bioinformatics analyses

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