scholarly journals Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?

2018 ◽  
Vol 56 (8) ◽  
pp. 521-525 ◽  
Author(s):  
Agostina Stradella ◽  
Jesús del Valle ◽  
Paula Rofes ◽  
Lídia Feliubadaló ◽  
Èlia Grau Garces ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Genes ◽  
Pathogenic Mutations ◽  
Predisposing Genes ◽  
Definition Of ◽  
Gene Panels

ImportanceGenetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.ObjectiveTo determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel.Patients and methodsA cohort of 1023 unrelated patients with suspicion of hereditary cancer was screened using a validated panel including up to 135 genes associated with hereditary cancer and phakomatoses.ResultsThirteen (1.37%) patients harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 5.7% (13/226) of patients with pathogenic mutations. Most (10/13) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene.Conclusions and relevanceGenetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.

A study of triple-negative breast cancer patients tested with a 25-gene panel of hereditary cancer genes.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1067-1067
Author(s):  
John F. Sandbach ◽  
Gayle Patel ◽  
Elisabeth King ◽  
Brent Evans ◽  
John Kidd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Hereditary Cancer ◽  
Triple Negative ◽  
Gene Panel ◽  
Cancer Genes ◽  
Breast Cancer Patients

scholarly journals Value of systematic genetic screening of patients with amyotrophic lateral sclerosis

2021 ◽  
pp. jnnp-2020-325014
Author(s):  
Stephanie R Shepheard ◽  
Matthew D Parker ◽  
Johnathan Cooper-Knock ◽  
Nick S Verber ◽  
Lee Tuddenham ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Age Of Onset ◽  
Clinical Care ◽  
Case Series ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Targeted Sequencing ◽  
Genetic Sequencing ◽  
Variant Of Uncertain Significance ◽  
Lateral Sclerosis

ObjectiveThe clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care.MethodsWe performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases.Results21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074).ConclusionsRoutine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients.

Outcomes of retesting BRCA-negative patients using multigene panels.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 23-23 ◽  
Author(s):  
Siddhartha Yadav ◽  
Jennifer Fulbright ◽  
Heidi Dreyfuss ◽  
Ashley Reeves ◽  
Sarah Campian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
New Technologies ◽  
Cancer Genetics ◽  
Pathogenic Mutation ◽  
Cancer Genes ◽  
Panel Testing ◽  
New Genes ◽  
Pathogenic Mutations ◽  
Potential Clinical Benefit

23 Background: New technologies for identifying hereditary predisposition to breast cancer have led to the discovery of novel genes associated with cancer risk. This has prompted re-evaluation of patients who previously tested negative for BRCA1/2 gene mutations, with a possibility of discovering new genes which may impact management. This study reports on the results of retesting patients who previously were negative for BRCA1/2. Methods: Patients who tested negative for BRCA1/2 mutations who had significant personal and family history were referred back to the Cancer Genetics Center between February 1, 2012 and May 30, 2105 for discussion of additional testing. A detailed personal and family history was reviewed, and patients were counseled about the genetics and clinical implications of panel testing for multiple breast cancer genes. Panel testing using next generation sequencing technologies was ordered. Patients were seen in follow up for discussion of results and management. Results: A total of 12 pathogenic mutations were identified during the study period. The genes and frequencies of these mutations were: CHEK2(3), PALB2(3), ATM(2), APC(1), BARD(1), CDH(1), MUTYH(1). There were 33 variants of undetermined significance(VUS) in 27 patients. 5 of these were seen in patients with a known pathogenic mutation; 3 others were later classified as benign. The frequencies of these VUSs were: ATM (9), PALB2(3), BARD1 (3), PTEN(3), PMS2(3), MSH6(2), CHEK2 (1), MYH(1), RAD51(1), BRIP1(2), NF1(1), BMPR1A(1). Of the 46 patients who had their initial BRCA testing and repeat panel testing between February 1, 2012 and May 30, 2015, 6 (13%) tested positive for a pathogenic mutation. Conclusions: This study demonstrates the feasibility and potential clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation. This approach had a significant management impact on patients and their families, with a 13% detection rate of pathogenic mutations. The success of retesting is predicated upon an infrastructure of provider and patient education, pre and post genetic counseling and serves as a model for other centers.

Frequency of germline patghogenic mutation in breast cancer patients at high risk hereditary cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13110-e13110 ◽  
Author(s):  
Hee-Chul Shin ◽  
Wonshik Han ◽  
Han-Byoel Lee ◽  
Hyeong-Gon Moon ◽  
Eunshin Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Hereditary Cancer ◽  
Gene Panel ◽  
Breast Cancer Patients ◽  
Sequencing Technology ◽  
Next Generation Sequencing Technology ◽  
Pathogenic Mutations ◽  
Generation Sequencing

e13110 Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel. Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64 gene panel, sequence variants were detected by next-generation sequencing technology. Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n = 9) or 3 (n = 1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n = 7), RET (n = 7), PTCH1 (n = 5), and MSH2 (n = 5) were the most prevalent pathogenic mutations. Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening.

scholarly journals A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes

Cancer ◽  
2017 ◽  
Vol 123 (10) ◽  
pp. 1721-1730 ◽  
Author(s):  
Saundra S. Buys ◽  
John F. Sandbach ◽  
Amanda Gammon ◽  
Gayle Patel ◽  
John Kidd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hereditary Cancer ◽  
Gene Panel ◽  
Cancer Genes

A study of ovarian cancer patients tested with a 25-gene panel of hereditary cancer genes.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1511-1511 ◽  
Author(s):  
Lucy R. Langer ◽  
Heidi McCoy ◽  
Kelsey Moyes ◽  
Jennifer Saam ◽  
Brian Abbott ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Hereditary Cancer ◽  
Gene Panel ◽  
Cancer Genes

scholarly journals Mutation prevalence tables for hereditary cancer derived from multi-gene panel testing

2019 ◽  
Author(s):  
Steven N. Hart ◽  
Eric C. Polley ◽  
Amal Yussuf ◽  
Siddhartha Yadav ◽  
David E. Goldgar ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Age Of Onset ◽  
Clinical Care ◽  
Cancer Predisposition ◽  
Gene Panel ◽  
High Risk Population ◽  
Cancer Type ◽  
Detection Rates ◽  
Panel Testing ◽  
Gene Panel Testing

AbstractPurposeMulti-gene panel testing for cancer predisposition mutations is becoming routine in clinical care. However, the gene content of panels offered by testing laboratories vary significantly, and data on mutation detection rates by gene and by panel is limited, causing confusion among clinicians on which test would be the most appropriate to order. Moreover, screening guidelines are not described in sufficient granularity to explain how differences in family, personal history, age, and other factors would affect the prevalence of finding a mutation in similar populations. The tool herein quantifies prevalence of mutations in hereditary cancer genes based on personalized clinical and demographic characteristics.MethodsUsing results from approximately 150,000 multi-gene panel tests conducted at Ambry Genetics, we built an interactive prevalence tool to explore how differences in ethnicity, age of onset, and personal and family history of different cancers affect the prevalence of pathogenic mutations in 31 cancer predisposition genes, across various clinically available hereditary cancer gene panels.ResultsOver 13,000 mutation carriers were identified in this high-risk population. Most of the cases were Non-Hispanic White (74%, n=109,537), but also provide an appreciable dataset for those identifying as Black (n=10,875), Ashkenazi Jewish (n=10,464), Hispanic (n=10,028), and Asian (n=7,090). The most prevalent cancer types were breast (50%), ovarian (6.6%), and colorectal (4.7%), which is expected based on genetic testing guidelines and clinician referral for testing.ConclusionThe Hereditary Cancer Multi-Gene Panel Prevalence Tool presented here can be used to provide insight into the prevalence of mutations on a per-gene and per-multigene panel basis, while conditioning on multiple custom phenotypic variables to include race and cancer type. The tool can be found at https://www.ambrygen.com/prevalence-tool.

A glance on dystonias, how to recognize and handle them

2019 ◽  
pp. 22-29
Author(s):  
F. N. Mercan ◽  
E. Bayram ◽  
M. C. Akbostanci
Keyword(s):  
Differential Diagnosis ◽  
Movement Disorder ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Body Part ◽  
Classification Model ◽  
Treatment Choices ◽  
Muscle Groups

Dystonia refers to an involuntary, repetitive, sustained, painful and twisting movements of the affected body part. This movement disorder was first described in 1911 by Hermain Oppenheim, and many studies have been conducted to understand the mechanism, the diagnosis and the treatment of dystonia ever since. However, there are still many unexplained aspects of this phenomenon. Dystonia is diagnosed by clinical manifestations, and various classifications are recommended for the diagnosis and the treatment. Anatomic classification, which is based on the muscle groups involved, is the most helpful classification model to plan the course of the treatment. Dystonias can also be classified based on the age of onset and the cause. These dystonic syndromes can be present without an identified etiology or they can be clinical manifestations of a neurodegenerative or neurometabolic disease. In this review we summarized the differential diagnosis, definition, classifications, possible mechanisms and treatment choices of dystonia.

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

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