scholarly journals Case report of a Li–Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2

Medicine ◽  
2016 ◽  
Vol 95 (49) ◽  
pp. e5665
Keyword(s):  
Case Report ◽  
De Novo ◽  
De Novo Mutation ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

scholarly journals Case report of a Li–Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2

Medicine ◽  
2016 ◽  
Vol 95 (29) ◽  
pp. e4251 ◽  
Author(s):  
Xuehan Zhuang ◽  
Yongping Li ◽  
Hongzhi Cao ◽  
Ting Wang ◽  
Jianghao Chen ◽  
...  
Keyword(s):  
Case Report ◽  
De Novo ◽  
De Novo Mutation ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

Identification and characterization of de novo TP53 mutation carriers in Li-Fraumeni syndrome families: A single institution experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10538-10538
Author(s):  
Carlos Christian Vera Recio ◽  
Jessica Corredor ◽  
Elissa Dodd-Eaton ◽  
Angelica M. Gutierrez-Barrera ◽  
Najat C. Daw ◽  
...  
Keyword(s):  
Tp53 Mutation ◽  
De Novo ◽  
De Novo Mutation ◽  
Brier Score ◽  
Li Fraumeni Syndrome ◽  
Mutation Carriers ◽  
Cancer Types ◽  
Li Fraumeni ◽  
Identification And Characterization

10538 Background: Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome mainly caused by a deleterious mutation in TP53. An estimated 48% of LFS patients present due to a deleterious de novo mutation (DNM) in TP53. The knowledge of DNM status, DNM or familial mutation (FM), of an LFS patient requires genetic testing of both parents which is often inaccessible, making de novo LFS patients an understudied population. Famdenovo.TP53 is a Mendelian Risk prediction model used to predict DNM status of TP53 mutation carriers based on the cancer-family history and several input genetic parameters, including disease-gene penetrance. The good predictive performance of Famdenovo.TP53 was demonstrated using data collected from four historical US cohorts. We hypothesize that by incorporating penetrance estimates that are specific for different types of cancers diagnosed in family members, we can develop a model with further improved calibration, accuracy and prediction. Methods: We present Famdenovo.CS, which uses cancer-specific penetrance estimates that were derived previously using a Bayesian semi-parametric competing risk model, to calculate the DNM probability. We use our model to analyze 101 families recently collected from the Clinical Cancer Genetic program at MD Anderson Cancer Center (CCG-TP53) that includes 20 families with known DNM status and 81 families with unknown DNM status. We used the concordance index (AUC), observed:expected ratios (OE) and Brier score (BS) to measure our model’s discrimination, calibration and accuracy, respectively. We estimate the proportion of probands that present a DNM and compare DNM to FM carriers in several areas including: cancer types diagnosed, age at diagnosis, number of primary cancers diagnosed, sex, amino acid change caused by mutation in TP53. Results: Famdenovo.CS showed equally good discrimination and calibration performance to Famdenovo.TP53, while improving the overall accuracy, demonstrated by a decrease in the Brier score of -0.09 (95% CI: [-0.02, -0.19]). Of the 101 probands in the CCG-TP53 cohort, we predict 39 to be DNMs and 62 to be FMs. The cancer types and ages of diagnosis observed in FMs and DNMs are similarly distributed. Conclusions: Famdenovo.CS shows improved model accuracy in the CCG cohort. DNMs in TP53 are a prevalent cause of LFS and we did not find differences in the clinical characteristics of DNM and FM carriers. Our model allows for a systematic identification and characterization of TP53 DNM carriers.

Li-Fraumeni syndrome and adrenal tumours: case report

2018 ◽  
Author(s):  
Mariana Tome ◽  
Jessica Guarino ◽  
Marta Iturregui
Keyword(s):  
Case Report ◽  
Li Fraumeni Syndrome ◽  
Adrenal Tumours ◽  
Li Fraumeni

scholarly journals A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report

2019 ◽  
Vol 10 ◽  
Author(s):  
Fengchang Qiao ◽  
Binbin Shao ◽  
Chen Wang ◽  
Yan Wang ◽  
Ran Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
De Novo ◽  
De Novo Mutation ◽  
Chinese Case

Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome

2017 ◽  
Vol 55 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Mariette Renaux-Petel ◽  
Françoise Charbonnier ◽  
Jean-Christophe Théry ◽  
Pierre Fermey ◽  
Gwendoline Lienard ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
De Novo ◽  
Multiple Primary Cancers ◽  
Breast Cancers ◽  
De Novo Mutations ◽  
Li Fraumeni Syndrome ◽  
Medical Laboratories ◽  
Li Fraumeni ◽  
Adrenocortical Carcinomas ◽  
Generation Sequencing

BackgroundDevelopment of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS.Methods and resultsAmong 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA by next-generation sequencing, performed at a depth above 500X, from 108 patients suggestive of LFS without detectable TP53 mutations, allowed us to identify 6 additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21 children with CPT, in 1/31 women with breast cancer before age 31 and in a patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast sarcoma at age 35.ConclusionsThis study performed on a large series of TP53 mutation carriers allows estimating the contribution to LFS of de novo mutations to at least 14% (48/336) and suggests that approximately one-fifth of these de novo mutations occur during embryonic development. Considering the medical impact of TP53 mutation identification, medical laboratories in charge of TP53 testing should ensure the detection of mosaic mutations.

scholarly journals Collagen-based biomaterials with possible therapeutic effects

2021 ◽  
pp. 324-329
Author(s):  
Ramona Nedelcuţă ◽  
Gigi Călin ◽  
Mihai Nedelcuţă ◽  
Vlad Baleanu ◽  
Dragos Davitoiu ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Disease ◽  
De Novo ◽  
De Novo Mutation ◽  
Stevens Johnson Syndrome ◽  
Therapeutic Effects ◽  
Enzymatic Process ◽  
Johnson Syndrome ◽  
Collagen Membranes ◽  
Definition Of

Epidermolysis bullosa (EB) is a rare, serious genetic disease, incurable through the current means. Apart from this initial definition, there was later some ease in the definition of the disease, including the manifestations of toxic epidermal necrolysis and Stevens Johnson syndrome in this entity. In medical practice, there are cases that do not overlap with the description in the literature, thus the treatment must be adapted and personalized to the particularities. We present the case of a female new-born, with "de novo" mutation for the early-onset antenatal epidermolysis and our personalized therapeutic management, based on collagen from bovine corneas by enzymatic process. The histological examination showed that the collagen membranes serve as a support for the epithelial cells that formed a surface monolayer after 48 hours. Therefore. this case report shows that collagen-based biomaterials could be used to accelerate the dermal-epidermal healing in various conditions of the child, such as Stevens Johnson syndrome, bullous epidermolysis and widespread burns.

scholarly journals Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

2019 ◽  
Author(s):  
Sofia Thunström ◽  
Markus Axelsson
Keyword(s):  
Case Report ◽  
Peripheral Neuropathy ◽  
De Novo ◽  
Age Of Onset ◽  
De Novo Mutation ◽  
Missense Mutations ◽  
Dural Ectasia ◽  
Whole Exome ◽  
Demyelinating Peripheral Neuropathy ◽  
Multiple Cysts

Abstract Background: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. Case Presentation: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686T>G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. Conclusions: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes. Keywords: Leukoencephalopathia, demyelinating peripheral neuropathy, dural ectasia explained, de novo mutation, the SAMD9L gene.

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