scholarly journals A combination of targeted enrichment methodologies for whole-exome sequencing reveals novel pathogenic mutations

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Fuyuki Miya ◽  
Mitsuhiro Kato ◽  
Tadashi Shiohama ◽  
Nobuhiko Okamoto ◽  
Shinji Saitoh ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pathogenic Mutations ◽  
Whole Exome ◽  
Targeted Enrichment

Burden of rare variants in causative genes for amyotrophic lateral sclerosis (ALS) accelerates age at onset of ALS

2018 ◽  
Vol 90 (5) ◽  
pp. 537-542 ◽  
Author(s):  
Hiroya Naruse ◽  
Hiroyuki Ishiura ◽  
Jun Mitsui ◽  
Yuji Takahashi ◽  
Takashi Matsukawa ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
Age At Onset ◽  
Sequencing Analysis ◽  
Pathogenic Mutations ◽  
Multiple Genes ◽  
Whole Exome ◽  
Lateral Sclerosis

ObjectivesTo evaluate the burden of rare variants in the causative genes for amyotrophic lateral sclerosis (ALS) on the age at onset of ALS in a Japanese case series.MethodsWe conducted whole-exome sequencing analysis of 89 families with familial ALS (FALS) and 410 patients with sporadic ALS (SALS) to identify known pathogenic mutations or rare functionally predicted deleterious variants in the causative genes for ALS. Rare variants (minor allele frequency <1%) with scaled Combined Annotation-Dependent Depletion score >20 were defined as rare functionally predicted deleterious variants. The patients with ALS were classified on the basis of the number of pathogenic and/or rare functionally predicted deleterious variants, and the age at onset was compared among the classified groups.ResultsWhole-exome sequencing analysis revealed known pathogenic mutations or rare functionally predicted deleterious variants in causative genes for ALS in 56 families with FALS (62.9%) and 87 patients with SALS (21.2%). Such variants in multiple genes were identified in seven probands with FALS and eight patients with SALS. The ages at onset in the patients with ALS with multiple variants were significantly earlier than those in other patients with ALS. Even when the patients with known pathogenic mutations were excluded, a significantly earlier onset of the disease was still observed in patients with multiple rare functionally predicted deleterious variants.ConclusionsA substantial number of patients carried rare variants in multiple genes, and the burden of rare variants in the known causative genes for ALS affects the age at onset in the Japanese ALS series.

scholarly journals Whole-exome sequencing in patients with protein aggregate myopathies reveals causative mutations associated with novel atypical phenotypes

2020 ◽  
Author(s):  
Marcin M. Machnicki ◽  
Valeria Guglielmi ◽  
Elia Pancheri ◽  
Francesca Gualandi ◽  
Lorenzo Verriello ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Degradation Products ◽  
Causative Role ◽  
Protein Aggregate ◽  
Causative Gene ◽  
Pathogenic Mutations ◽  
Whole Exome ◽  
Genes Encoding ◽  
Associated Proteins

Abstract Background Myofibrillar myopathies (MFM) are a subgroup of protein aggregate myopathies (PAM) characterized by a common histological picture of myofibrillar dissolution, Z-disk disintegration, and accumulation of degradation products into inclusions. Mutations in genes encoding components of the Z-disk or Z-disk-associated proteins occur in some patients whereas in most of the cases, the causative gene defect is still unknown. We aimed to search for pathogenic mutations in genes not previously associated with MFM phenotype. Methods We performed whole-exome sequencing in four patients from three unrelated families who were diagnosed with PAM without aberrations in causative genes for MFM. Results In the first patient and her affected daughter, we identified a heterozygous p.(Arg89Cys) missense mutation in LMNA gene which has not been linked with PAM pathology before. In the second patient, a heterozygous p.(Asn4807Phe) mutation in RYR1 not previously described in PAM represents a novel, candidate gene with a possible causative role in the disease. Finally, in the third patient and his symptomatic daughter, we found a previously reported heterozygous p.(Cys30071Arg) mutation in TTN gene that was clinically associated with cardiac involvement. Conclusions Our study identifies a new genetic background in PAM pathology and expands the clinical phenotype of known pathogenic mutations.

Whole Exome Sequencing (WES) in Familien mit linksventrikulärer Ausfluβtraktobstruktion (LVOTO)

2014 ◽  
Vol 62 (S 02) ◽  
Author(s):  
M. Hitz ◽  
S. Al-Turki ◽  
A. Schalinski ◽  
U. Bauer ◽  
T. Pickardt ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

FV 1031. Whole Exome Sequencing for Children with Dyskinetic Movement Disorder

2018 ◽  
Author(s):  
Yasemin Dincer ◽  
Michael Zech ◽  
Matias Wagner ◽  
Nikolai Jung ◽  
Volker Mall ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome ◽  
Dyskinetic Movement
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