Small mutation screening in the DMD gene by whole exome sequencing of an Argentine Duchenne/Becker muscular dystrophies cohort

2018 ◽  
Vol 28 (12) ◽  
pp. 986-995 ◽  
Author(s):  
Leonela N. Luce ◽  
Micaela Carcione ◽  
Chiara Mazzanti ◽  
Marcela Ferrer ◽  
Irene Szijan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mutation Screening ◽  
Muscular Dystrophies ◽  
Whole Exome ◽  
Dmd Gene

Whole Exome Sequencing for Mutation Screening in Hemophagocytic Lymphohistiocytosis

2020 ◽  
Author(s):  
Edris Sharif Rahmani ◽  
Majid Fathi ◽  
Mohammad Foad Abazari ◽  
Hojat Shahraki ◽  
Vahid Ziaee Fellow ◽  
...  
Keyword(s):  
Immune System ◽  
Data Analysis ◽  
Exome Sequencing ◽  
Molecular Characterization ◽  
Whole Exome Sequencing ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Mutation Screening ◽  
Positive Family History ◽  
Whole Exome

Background: Hemophagocytic lymphohistiocytosis (HLH) is an immune system disorder characterized by uncontrolled hyper-inflammation owing to hypercytokinemia from the activated but ineffective cytotoxic cells. Establishing a correct diagnosis for HLH patients due to the similarity of this disease with other conditions like malignant lymphoma and leukemia and similarity among its two forms is difficult and not always a successful procedure. Besides, the molecular characterization of HLH due to the locus and allelic heterogeneity is a challenging issue. Materials and Methods: In this experimental study, whole exome sequencing (WES) was used for mutation detection in a four-member Iranian family with children suffering from signs and symptoms of HLH disease. Data analysis was performed by using a multi-step in-house WES approach on Linux OS. Result: In this study, a homozygous nucleotide substitution mutation (c.551G>A:p.W184*) was detected in exon number six of the UNC13D gene. W184* drives to a premature stop codon, so produce a truncated protein. This mutation inherited from parents to a four-month female infant with an autosomal recessive pattern. Parents were carrying out the heterozygous form of W184* without any symptoms. The patient showed clinical signs such as fever, diarrhea, hepatosplenomegaly, high level of ferritin, and a positive family history of HLH disease. W184* has a damaging effect on cytotoxic T lymphocytes, and natural killer cells. These two types of immune system cells without a healthy product of the UNC13D gene will be unable to discharge toxic granules into the synaptic space, so the inflammation in the immune response does not disappear. Conclusion: According to this study, WES can be a reliable, fast, and cost-effective approach for the molecular characterization of HLH patients. Plus, WES specific data analysis platform introduced by this study potentially offers a high-speed analysis step. This cost-free platform doesn't require online data submission.

Gene mutation screening using whole exome sequencing in lipid storage myopathy

2015 ◽  
Vol 25 ◽  
pp. S204
Author(s):  
K. Takayama ◽  
S. Mitsuhashi ◽  
I. Nonaka ◽  
S. Noguchi ◽  
I. Nishino
Keyword(s):  
Exome Sequencing ◽  
Gene Mutation ◽  
Whole Exome Sequencing ◽  
Mutation Screening ◽  
Lipid Storage ◽  
Lipid Storage Myopathy ◽  
Whole Exome

COL4A1 and COL4A2 Mutations Analyses with Perinatal Arterial İschemic Stroke

2020 ◽  
Author(s):  
Ozan Koçak ◽  
Kursat Bora Carman Bora Carman ◽  
Coskun Yarar ◽  
Hirofumi Kodera ◽  
Hirotomo Saitsu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Small Vessel Disease ◽  
Mutation Screening ◽  
Laboratory Data ◽  
Sequencing Analysis ◽  
Arterial Ischemic Stroke ◽  
Whole Exome ◽  
Perinatal Arterial Ischemic Stroke

Perinatal arterial ischemic stroke (PAIS) is one of the frequent causes of mortality and morbidity, but its etiology remains unclear. COL4A1 and COL4A2 mutations are monogenetic causes of weakness of the basement vascular membranes resulting in cerebral small-vessel disease, cerebral hemorrhage, and porencephaly. We hypothesized that variations in the COL4A1 and COL4A2 genes cause PAIS and performed mutation screening of these genes in 17 PAIS patients by whole-exome sequencing. Clinical, demographic, and laboratory data of the 17 PAIS patients were obtained by evaluating hospital files retrospectively. Patients included in the study were invited to the clinic for COL4A1 and COL4A2 mutation analysis. Results: The patient group consisted of 13 females (76.5%) and four males (23.5%) with a mean age of 107.4 ± 11.5 months. Maternal/fetal and prothrombotic risk factors identified in 52.9% and 94.1% of the patients, respectively. Whole-exome sequencing analysis did not reveal COL4A1 and COL4A2 pathological mutations in any of the patients.  Although we did not find an association between PAIS and COL4A1 and COL4A2 variations, we believe that new studies with larger patient populations may reveal such a relationship.

Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings

2017 ◽  
Vol 32 (10) ◽  
pp. 867-870 ◽  
Author(s):  
Hannah Song ◽  
Sina Haeri ◽  
Hannes Vogel ◽  
Marjo van der Knaap ◽  
Keith Van Haren
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Care ◽  
Mutation Screening ◽  
Medical Decision ◽  
Homozygous Mutation ◽  
Vitro Fertilization ◽  
Whole Exome ◽  
The Impact

Objective: We describe 2 male siblings with a severe, prenatal phenotype of vanishing white matter disease and the impact of whole exome sequencing on their diagnosis and clinical care. Methods: The 2 children underwent detailed clinical characterization, through clinical and laboratory testing, as well as prenatal and postnatal imaging. Biobanked blood from the 2 siblings was submitted for whole exome sequencing at Baylor Laboratories. Results: Both male children had abnormal prenatal neuroimaging and suffered precipitous, fatal neurologic decline. Neuropathologic findings included subependymal pseudocysts, microcalcifications, and profound lack of brain myelin and sparing of peripheral nerve myelin. A novel homozygous mutation in the EIF2B3 gene (c.97A>G [p.Lys33Glu]) was found in both children; both parents were heterozygous carriers. The family subsequently conceived a healthy child via in vitro fertilization with preimplantation mutation screening. Conclusion: These histories expand the prenatal phenotype of eIF2b-related disorders and poignantly illustrate the impact that unbiased genomic sequencing can have on the diagnosis and medical decision making for families affected by childhood neurodegenerative disorders.

scholarly journals Whole exome sequencing revealed a mutation in COL6A1 associated with ullrich congenital muscular dystrophy

2021 ◽  
Vol 19 (2) ◽  
pp. 213-221
Author(s):  
Dinh Huong Thao ◽  
Nguyen Phuong Anh ◽  
Noriko Miyake ◽  
Nong Van Hai ◽  
Naomichi Matsumoto ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Congenital Muscular Dystrophy ◽  
Pulmonary Insufficiency ◽  
Muscular Dystrophies ◽  
Whole Exome ◽  
Ullrich Congenital Muscular Dystrophy ◽  
Standing Up ◽  
Normal Cognitive Function ◽  
Distal Joint

Collagen type VI-related disorders consist of Ullrich congenital muscular dystrophies (UCMD) and Bethlem myopathy, in which these entities are at two opposite extremes of the phenotype continuum. Clinical characteristics include proximal joint contracture, distal joint hyperlaxity, generalized muscle weakness, normal cognitive function, and pulmonary insufficiency. Affected individuals have trouble standing up and walking independently. Mutations in 3 genes (COL6A1, COL6A2, and COL6A3) are associated with decreasing collagen-VI production and disrupting the microfibrillar network between skeletal muscles. In the present study, using whole-exome sequencing (WES), a pathogenic variant in the COL6A1 gene (NM_001848, c.868G>C, p.G290R) was detected in a Vietnamese family with UCMD patients. Segregation analysis by Sanger sequencing confirmed that this mutation was inherited in an autosomal dominant pattern. This study expands the breadth of congenital muscular dystrophies research landcape and underscores the efficiency of WES in investigating the etiology of this group of heterogeneous diseases. Insight about the underlying genetic causes could contribute to develop a well-timed treatment regimen and help patients make an informed decision about reproductive health. 

Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic mutation

Neurology ◽  
2018 ◽  
Vol 90 (7) ◽  
pp. e575-e582 ◽  
Author(s):  
Nadine Pelzer ◽  
Joost Haan ◽  
Anine H. Stam ◽  
Lisanne S. Vijfhuizen ◽  
Stephany C. Koelewijn ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Characteristics ◽  
Autosomal Dominant ◽  
Mutation Screening ◽  
Dominant Gene ◽  
Hemiplegic Migraine ◽  
Mild Phenotype ◽  
New Genes ◽  
Whole Exome

ObjectiveTo investigate whether the clinical characteristics of patients with hemiplegic migraine with and without autosomal dominant mutations in CACNA1A, ATP1A2, or SCN1A differ, and whether the disease may be caused by mutations in other genes.MethodsWe compared the clinical characteristics of 208 patients with familial (n = 199) or sporadic (n = 9) hemiplegic migraine due to a mutation in CACNA1A, ATP1A2, or SCN1A with those of 73 patients with familial (n = 49) or sporadic (n = 24) hemiplegic migraine without a mutation in these genes. In addition, 47 patients (familial: n = 33; sporadic: n = 14) without mutations in CACNA1A, ATP1A2, or SCN1A were scanned for mutations in novel genes using whole exome sequencing.ResultsPatients with mutations in CACNA1A, ATP1A2, or SCN1A had a lower age at disease onset, larger numbers of affected family members, and more often attacks (1) triggered by mild head trauma, (2) with extensive motor weakness, and (3) with brainstem features, confusion, and brain edema. Mental retardation and progressive ataxia were exclusively found in patients with a mutation. Whole exome sequencing failed to identify pathogenic mutations in new genes.ConclusionsMost patients with hemiplegic migraine without a mutation in CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of common (nonhemiplegic) migraine. A major fourth autosomal dominant gene for hemiplegic migraine remains to be identified. Our observations might guide physicians in selecting patients for mutation screening and in providing adequate genetic counseling.

scholarly journals Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Adiratna Mat Ripen ◽  
Mei Yee Chiow ◽  
Prakash Rao Rama Rao ◽  
Saharuddin Bin Mohamad
Keyword(s):  
Chronic Granulomatous Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Disorder ◽  
Mutation Screening ◽  
Copy Number Variations ◽  
Granulomatous Disease ◽  
Inborn Errors ◽  
Exon 2 ◽  
Whole Exome

Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1-to-NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1. Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment.

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