scholarly journals Compound heterozygous variants including a novel copy number variation in a child with atypical ataxia-telangiectasia: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hoo Young Lee ◽  
Dae-Hyun Jang ◽  
Jae-Won Kim ◽  
Dong-Woo Lee ◽  
Ja-Hyun Jang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Ataxia Telangiectasia ◽  
Single Nucleotide Polymorphism Array ◽  
Compound Heterozygous ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Variants ◽  
Number Variation ◽  
Generation Sequencing

Abstract Background Ataxia-telangiectasia is a rare autosomal recessive, neurodegenerative disorder caused by alterations in the ATM gene. The majority of ATM pathogenic variants are frameshift or nonsense variants which are predicted to truncate the whole ATM protein. Herein, we report on an ataxia telangiectasia child with atypical phenotype who was identified as compound heterozygous for two ATM variants involving a previously described pathogenic single nucleotide variation (SNV) and a novel copy number variation (CNV). Case presentation A 6-year-old boy presented with delayed development and oculomotor apraxia. Brain magnetic resonance imaging showed interval development of mild atrophy in the cerebellum. Serum alpha fetoprotein level was in normal range. Next-generation sequencing and single-nucleotide polymorphism array tests were performed. Next-generation sequencing revealed a heterozygous nonsense pathogenic variant in ATM, c.742C > T (p.Arg248Ter) inherited from the father. Single-nucleotide polymorphism array revealed a compound heterozygous CNV, arr[GRCh37] 11q22.3(10851766–108183226) × 1, 31460 bp (exons 24–40 deletion of ATM) inherited from the mother, which was validated by reverse transcription-polymerase chain reaction analysis (RT-PCR). We demonstrated that this variant (NM_000051.4:c.3403_6006del) generated a product of in-frame deletion of exon 24–40 of ATM (p.Ser1135_Gln2002del). Conclusions The compound heterozygosity for ATM variants involving a previously described pathogenic SNV and a novel CNV may be associated with the atypical clinical manifestations. This clinical report extends the genetic and phenotypic spectrum of ATM pathogenic variants in atypical ataxia-telangiectasia, thus making implementation of advanced analysis beyond the routine next-generation sequencing an important consideration in diagnosis and rehabilitation services for children with ataxia-telangiectasia.

scholarly journals High concordance between next generation sequencing and single-nucleotide polymorphism array in preimplantation genetic testing for aneuploid

2020 ◽  
Author(s):  
Zhanhui Ou ◽  
Zhiheng Chen ◽  
Yu Deng ◽  
Minna Yin ◽  
Ling Sun
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Next Generation Sequencing ◽  
Single Nucleotide Polymorphism Array ◽  
Snp Array ◽  
Concordance Rate ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
High Concordance ◽  
Generation Sequencing

Abstract Background: Single-nucleotide polymorphism array (SNP array) and next generation sequencing (NGS) in detecting chromosome aneuploidy are widely used in clinical work. Aims: To compare the concordance between NGS and SNP array in 67 embryos (from 23 couples). Methods: In the first part of the study, 28 blastocysts with unknown ploidy were both analyzed with NGS and SNP array. While in the second part, 39 with normal ploidy detected by NGS were re-analyzed with SNP array. Results: In the first part of the study, the concordance rate between NGS and SNP array was 92.9% (26/28). Among the 28 blastocysts, 18 were abnormal and 10 blastocysts were with normal ploidy status when analyzed by NGS. Among the 18 abnormal blastocysts, two blastocysts were with low level of mosaicism as analyzed by NGS, but euploid with SNP array. In the second part, concordance rate between NGS and SNP array was 100% (39/39). At last, one couple had no blastocyst to transfer. The other 22 couples were transferred with single blastocyst. Among them, two couples suffered abortions before 12 weeks, and the karyotype of villus was normal. One couple with only 1 normal blastocyst failed to conceive after the transfer. In total nineteen couples had healthy babies born. Conclusions: There was a high concordance rate between NGS and SNP array. But NGS was also able to detect mosaicism sensitively. Hence, using NGS for PGT-A may increase the chances of having a healthy and live newborn child.

Screening of genetic variants in ELANE mutation negative congenital neutropenia by next generation sequencing

2019 ◽  
Vol 73 (6) ◽  
pp. 322-327 ◽  
Author(s):  
Arun Kumar Arunachalam ◽  
Hemamalini Suresh ◽  
Eunice Sindhuvi Edison ◽  
Anu Korula ◽  
Fouzia N Aboobacker ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Bacterial Infections ◽  
Clinical Severity ◽  
Causative Mutation ◽  
Compound Heterozygous ◽  
Inherited Disease ◽  
Next Generation ◽  
Congenital Neutropenia ◽  
Pathogenic Variants ◽  
Generation Sequencing

AimsCongenital neutropenia (CN) is a rare inherited disease that results in recurrent, life-threatening bacterial infections due to a deficiency of mature neutrophils. They are usually caused by heterozygous ELANE mutations although mutations in other genes like HAX-1, G6PC3 and GFI1 have also been reported. Identifying the causative mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia like autoimmune cytopenia and evolving aplasia. We aimed to identify the molecular defects in CN patients who had no mutations in ELANE gene, by next generation sequencing (NGS) targeting a customised panel of genes.MethodsDNA samples were sequenced with an Illumina NextSeq sequencer using an in-house customised panel of genes at ≥100× depth. Bioinformatics analysis was carried out and the pathogenic variants were identified using a stepwise filtering and analysis strategy. Specific mutations identified were subsequently validated by Sanger sequencing.ResultsThe pathogenic variants identified in the study includes previously reported variants in SBDS (compound heterozygous c.258+2T>C and c.1A>T), GATA2 (heterozygous c.1186C>T) and novel variants in WAS (hemizygous c.812T>C), JAGN1 (homozygous c.70G>A) and RTEL1 (heterozygous c.2893G>C) genes.ConclusionThis study highlights that the absence of ELANE mutations does not rule out the diagnosis of CN and this NGS based approach with a customised panel will help in diagnostic confirmation in such patients. The early onset of the disease, clinical severity and associated high risk of malignant transformation in CN strongly suggests the need for early diagnosis and therapeutic intervention.

scholarly journals Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Abinaya Manivannan ◽  
Jin-Hee Kim ◽  
Eun-Young Yang ◽  
Yul-Kyun Ahn ◽  
Eun-Su Lee ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Disease Resistance ◽  
Next Generation Sequencing ◽  
Molecular Mechanisms ◽  
Next Generation ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genome Wide ◽  
The Impact ◽  
Generation Sequencing

Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS) approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding. The availability of genomic information aids in the deeper understanding of several molecular mechanisms behind the vital physiological processes. In addition, the NGS methods facilitate the genome-wide discovery of DNA based markers linked to key genes involved in important biological phenomenon. Among the molecular markers, single nucleotide polymorphism (SNP) indulges various benefits in comparison with other existing DNA based markers. The present review concentrates on the impact of NGS approaches in the discovery of useful SNP markers associated with pungency and disease resistance in pepper. The information provided in the current endeavor can be utilized for the betterment of pepper breeding in future.

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