Genetic counseling for early onset and familial dementia: Patient perspectives on exome sequencing

2021 ◽  
Author(s):  
Bradley Rolf ◽  
Elizabeth E. Blue ◽  
Stephanie Bucks ◽  
Michael O. Dorschner ◽  
Suman Jayadev
Keyword(s):  
Genetic Counseling ◽  
Exome Sequencing ◽  
Early Onset ◽  
Patient Perspectives ◽  
Dementia Patient ◽  
Familial Dementia

Utility and implications of exome sequencing in early‐onset Parkinson's disease

2018 ◽  
Vol 34 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Joanne Trinh ◽  
Katja Lohmann ◽  
Hauke Baumann ◽  
Alexander Balck ◽  
Max Borsche ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exome Sequencing ◽  
Early Onset ◽  
Early Onset Parkinson’S Disease

scholarly journals A Novel Homozygous In-Frame Deletion in Complement Factor 3 Underlies Early-Onset Autosomal Recessive Atypical Hemolytic Uremic Syndrome - Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Shirley Pollack ◽  
Israel Eisenstein ◽  
Adi Mory ◽  
Tamar Paperna ◽  
Ayala Ofir ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Exome Sequencing ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Critical Role ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complement Factor ◽  
Complement Components ◽  
Uremic Syndrome ◽  
Close Relatives

Background and ObjectivesAtypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. Hereditary aHUS due to C3 disruption is rare, usually caused by heterozygous activating mutations in the C3 gene, and transmitted as autosomal dominant traits. We studied the molecular basis of early-onset aHUS, associated with an unusual finding of a novel homozygous activating deletion in C3.Design, Setting, Participants, & MeasurementsA male neonate with eculizumab-responsive fulminant aHUS and C3 hypocomplementemia, and six of his healthy close relatives were investigated. Genetic analysis on genomic DNA was performed by exome sequencing of the patient, followed by targeted Sanger sequencing for variant detection in his close relatives. Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother.ResultsExome sequencing revealed a novel homozygous variant in exon 26 of C3 (c.3322_3333del, p.Ile1108_Lys1111del), within the highly conserved thioester-containing domain (TED), fully segregating with the familial disease phenotype, as compatible with autosomal recessive inheritance. Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack complex, while his healthy heterozygous mother showed intermediate levels of C3 consumption.ConclusionsOur findings represent the first description of aHUS secondary to a novel homozygous deletion in C3 with ensuing unbalanced C3 over-activation, highlighting a critical role for the disrupted C3-TED domain in the disease mechanism.

scholarly journals Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons

2015 ◽  
Vol 24 (5) ◽  
pp. 710-716 ◽  
Author(s):  
Gaël Nicolas ◽  
David Wallon ◽  
Camille Charbonnier ◽  
Olivier Quenez ◽  
Stéphane Rousseau ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Whole Exome

scholarly journals Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing

2018 ◽  
Vol 9 ◽  
Author(s):  
Mathias Cavaillé ◽  
Flora Ponelle-Chachuat ◽  
Nancy Uhrhammer ◽  
Sandrine Viala ◽  
Mathilde Gay-Bellile ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Cowden Syndrome ◽  
Atypical Presentation ◽  
Primary Tumors ◽  
Multiple Primary Tumors ◽  
Whole Exome ◽  
Multiple Primary

scholarly journals CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease

2019 ◽  
Vol 25 (11) ◽  
pp. 1788-1795 ◽  
Author(s):  
Thomas Magg ◽  
Anna Shcherbina ◽  
Duran Arslan ◽  
Mukesh M Desai ◽  
Sarah Wall ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Loss Of Function ◽  
Peripheral Blood Mononuclear ◽  
Whole Exome ◽  
Inflammatory Bowel

Abstract Background Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes. Methods To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID. Results Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency. Conclusion Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.

scholarly journals Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy

2019 ◽  
Vol 10 ◽  
Author(s):  
Michelle Demos ◽  
Ilaria Guella ◽  
Conrado DeGuzman ◽  
Marna B. McKenzie ◽  
Sarah E. Buerki ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Early Onset ◽  
Diagnostic Yield ◽  
Targeted Exome Sequencing

scholarly journals Whole exome sequencing identifies FBN1 mutations in two patients with early-onset type B aortic dissection

2017 ◽  
Vol 16 (5) ◽  
pp. 6620-6625
Author(s):  
Qian Han ◽  
Wenwen Zhang ◽  
Changjian Liu ◽  
Min Zhou ◽  
Feng Ran ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Type B ◽  
Type B Aortic Dissection ◽  
Onset Type ◽  
Whole Exome
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