Mitochondrial DNA analysis from exome sequencing data improves the diagnostic yield in neurological diseases

AbstractExome sequencing is a powerful tool for detecting both single and multiple nucleotide variation genome wide. However long indels, in the size range 20 – 200bp, remain difficult to accurately detect. By assessing a set of common exonic long indels, we estimate the sensitivity of long indel detection in exome sequencing data to be 92%. To clarify the role of pathogenic long indels in patients with intellectual disability (ID), we analysed exome sequencing data from 820 patients using two variant callers, Pindel and Platypus. We identified three indels explaining the patients’ clinical phenotype by disrupting the UBE3A, PGAP3 and MECP2 genes. Comparison of different tools demonstrated the importance of both correct genotyping and annotation variants. In conclusion, specialized long indel detection can improve diagnostic yield in ID patients.

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Deciphering exome sequencing data: Bringing mitochondrial DNA variants to light

Human Mutation ◽

10.1002/humu.23885 ◽

2019 ◽

Vol 40 (12) ◽

pp. 2430-2443 ◽

Cited By ~ 1

Author(s):

Philippine Garret ◽

Céline Bris ◽

Vincent Procaccio ◽

Patrizia Amati‐Bonneau ◽

Pierre Vabres ◽

...

Keyword(s):

Mitochondrial Dna ◽

Exome Sequencing ◽

Sequencing Data ◽

Exome Sequencing Data ◽

Dna Variants ◽

Mitochondrial Dna Variants

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AQME: A forensic mitochondrial DNA analysis tool for next-generation sequencing data

Forensic Science International Genetics ◽

10.1016/j.fsigen.2017.09.010 ◽

2017 ◽

Vol 31 ◽

pp. 189-197 ◽

Cited By ~ 16

Author(s):

Kimberly Sturk-Andreaggi ◽

Michelle A. Peck ◽

Cecilie Boysen ◽

Patrick Dekker ◽

Timothy P. McMahon ◽

...

Keyword(s):

Mitochondrial Dna ◽

Next Generation Sequencing ◽

Dna Analysis ◽

Next Generation Sequencing Data ◽

Analysis Tool ◽

Next Generation ◽

Sequencing Data ◽

Mitochondrial Dna Analysis ◽

Generation Sequencing

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Delineation of Mitochondrial DNA Variants From Exome Sequencing Data and Association of Haplogroups With Obesity in Kuwait

Frontiers in Genetics ◽

10.3389/fgene.2021.626260 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mohammed Dashti ◽

Hussain Alsaleh ◽

Muthukrishnan Eaaswarkhanth ◽

Sumi Elsa John ◽

Rasheeba Nizam ◽

...

Keyword(s):

Mitochondrial Dna ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sequencing Data ◽

Arab Population ◽

Exome Sequencing Data ◽

Sequencing Technologies ◽

Whole Exome ◽

Dna Variants ◽

Mitochondrial Dna Variants

Background/ObjectivesWhole-exome sequencing is a valuable tool to determine genetic variations that are associated with rare and common health conditions. A limited number of studies demonstrated that mitochondrial DNA can be captured using whole-exome sequencing. Previous studies have suggested that mitochondrial DNA variants and haplogroup lineages are associated with obesity. Therefore, we investigated the role of mitochondrial variants and haplogroups contributing to the risk of obesity in Arabs in Kuwait using exome sequencing data.Subjects/MethodsIndirect mitochondrial genomes were extracted from exome sequencing data from 288 unrelated native Arab individuals from Kuwait. The cohort was divided into obese [body mass index (BMI) ≥ 30 kg/m2] and non-obese (BMI < 30 kg/m2) groups. Mitochondrial variants were identified, and haplogroups were classified and compared with other sequencing technologies. Statistical analysis was performed to determine associations and identify mitochondrial variants and haplogroups affecting obesity.ResultsHaplogroup R showed a protective effect on obesity [odds ratio (OR) = 0.311; P = 0.006], whereas haplogroup L individuals were at high risk of obesity (OR = 2.285; P = 0.046). Significant differences in mitochondrial variants between the obese and non-obese groups were mainly haplogroup-defining mutations and were involved in processes in energy generation. The majority of mitochondrial variants and haplogroups extracted from exome were in agreement with technical replica from Sanger and whole-genome sequencing.ConclusionsThis is the first to utilize whole-exome data to extract entire mitochondrial haplogroups to study its association with obesity in an Arab population.

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Leber Hereditary Optic Neuropathy - Idebenone, Hope of Treatment

Revista de Chimie ◽

10.37358/rc.19.12.7740 ◽

2020 ◽

Vol 70 (12) ◽

pp. 4244-4247

Keyword(s):

Mitochondrial Dna ◽

Visual Field ◽

Optic Neuropathy ◽

Mitochondrial Function ◽

Dna Analysis ◽

Central Vision ◽

Leber Hereditary Optic Neuropathy ◽

Mitochondrial Dna Analysis ◽

Hereditary Optic Neuropathy

Leber hereditary optical neuropathy (LHON) is part of the class of optic neuropathies in which the mitochondrial function is impaired and is characterized by a painless, subacute, bilateral decrease of the central vision. We shall present the case of two brothers AM aged 31 and AT aged 40 who were diagnosed with LHON and whom we initiated treatment with idebenone 900 mg / day with monitoring at one month and 6 months. The mitochondrial DNA analysis demonstrated the existence of mutations 11778G>A for the mtND4 gene in both patients. Idebenone is a synthetic benzoquinone, analogue of ubiquinone. We found a slight but significant improvement in the visual field in patient AM at one month of treatment. We have not found another case in the literature with an improvement in vision so fast after this treatment, and this has led us to write this article. Keywords: Leber hereditary optical neuropathy (LHON), idebenone, mutations 11778G>A, mtND4 gene

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Exome sequencing in paediatric patients with movement disorders

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01688-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Anna Ka-Yee Kwong ◽

Mandy Ho-Yin Tsang ◽

Jasmine Lee-Fong Fung ◽

Christopher Chun-Yu Mak ◽

Kate Lok-San Chan ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Movement Disorders ◽

Rare Variants ◽

Diagnostic Yield ◽

Neurological Diseases ◽

Genetic Diagnosis ◽

Potential Treatment ◽

Paediatric Patients ◽

Whole Exome

Abstract Background Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusions A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

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