Whole exome sequencing shows oligogenic inheritance as a pathogenic mechanism for an atypical Leigh syndrome in a pediatric patient

2021 ◽  
Vol 132 ◽  
pp. S5-S6
Author(s):  
Kuntal Sen ◽  
Martine Uittenbogaard ◽  
Yue Wang ◽  
Andrea Gropman ◽  
Anne Chiaramello
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Patient ◽  
Leigh Syndrome ◽  
Pathogenic Mechanism ◽  
Whole Exome ◽  
Oligogenic Inheritance

scholarly journals Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hosneara Akter ◽  
Mohammad Shahnoor Hossain ◽  
Nushrat Jahan Dity ◽  
Md. Atikur Rahaman ◽  
K. M. Furkan Uddin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diseases ◽  
Leigh Syndrome ◽  
Genetic Profile ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Rare Genetic Diseases ◽  
Compound Heterozygous Variants

AbstractCollectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet–Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.

scholarly journals Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French–Canadian Type Outside of Québec

2017 ◽  
Vol 4 ◽  
pp. 2329048X1773763 ◽  
Author(s):  
Velda Xinying Han ◽  
Teresa S. Tan ◽  
Furene S. Wang ◽  
Stacey Kiat-Hong Tay
Keyword(s):  
Cytochrome C ◽  
Exome Sequencing ◽  
Cytochrome C Oxidase ◽  
Whole Exome Sequencing ◽  
Genetic Disorder ◽  
Leigh Syndrome ◽  
Compound Heterozygous ◽  
French Canadian ◽  
Metabolic Crisis ◽  
Whole Exome

Background: Leigh syndrome, French–Canadian type is unique to patients from a genetic isolate in the Saguenay–Lac-Saint-Jean region of Québec. It has also been recently described in 10 patients with LRPPRC mutation outside of Québec. It is an autosomal recessive genetic disorder with fatal metabolic crisis and severe neurological morbidity in infancy caused by LRPPRC mutation. Methods and Results: The authors report a boy with a novel LRPPRC compound heterozygous missense mutations c.3130C>T, c.3430C>T, and c.4078G>A found on whole-exome sequencing which correlated with isolated cytochrome c-oxidase deficiency found in skeletal muscle. Conclusion: LRPPRC mutation is a rare cause of cytochrome c-oxidase–deficient form of Leigh syndrome outside of Québec. Our patient broadens the spectrum of phenotypes of Leigh syndrome, French–Canadian type. LRPPRC mutation should be considered in children with early childhood neurodegenerative disorder, even in the absence of metabolic crisis. Early evaluation with whole-exome sequencing is useful for early diagnosis and for genetic counseling.

scholarly journals Novel ECHS1 mutations in Leigh syndrome identified by whole-exome sequencing in five Chinese families: case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dan Sun ◽  
Zhimei Liu ◽  
Yongchu Liu ◽  
Miaojuan Wu ◽  
Fang Fang ◽  
...  
Keyword(s):  
Case Report ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Leigh Syndrome ◽  
Chinese Families ◽  
Whole Exome

Leigh syndrome caused by mitochondrial DNA-maintenance defects revealed by whole exome sequencing

Mitochondrion ◽  
2019 ◽  
Vol 49 ◽  
pp. 25-34 ◽  
Author(s):  
P.V.S. Souza ◽  
Thiago Bortholin ◽  
Carlos Alberto Castro Teixeira ◽  
Daniel Delgado Seneor ◽  
Vitor Dias Gomes Barrios Marin ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Leigh Syndrome ◽  
Whole Exome ◽  
Dna Maintenance

Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome

2015 ◽  
Vol 134 (9) ◽  
pp. 981-991 ◽  
Author(s):  
Martine Tetreault ◽  
◽  
Somayyeh Fahiminiya ◽  
Hana Antonicka ◽  
Grant A. Mitchell ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Leigh Syndrome ◽  
Whole Exome

scholarly journals Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Maria Carolina Ortube ◽  
Samuel P Strom ◽  
Stanley F Nelson ◽  
Steven Nusinowitz ◽  
Ariadna Martinez ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Whole Exome Sequencing ◽  
Pediatric Patient ◽  
Retinal Dystrophy ◽  
Whole Exome

scholarly journals Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

2020 ◽  
Vol 24 (6) ◽  
pp. 400-403
Author(s):  
Rasoul Alizadeh ◽  
Sanaz Jamshidi ◽  
Mohammad Keramatipour ◽  
Parisa Moeinian ◽  
Rozita Hosseini ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Patient ◽  
Novel Mutation ◽  
Whole Exome

Specific Cognitive Changes due to Hippocalcin Alterations? A Novel Familial Homozygous Hippocalcin Variant Associated with Inherited Dystonia and Altered Cognition

2021 ◽  
Author(s):  
Sandy Siegert ◽  
Wolfgang M. Schmidt ◽  
Thomas Pletschko ◽  
Reginald E. Bittner ◽  
Sonja Gobara ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Patient ◽  
Autosomal Recessive ◽  
Family Members ◽  
Missense Variant ◽  
Index Patient ◽  
Cognitive Changes ◽  
Her Family ◽  
Whole Exome

Abstract Background Recent research suggested an hippocalcin (HPCA)-related form of DYT2-like autosomal recessive dystonia. Two reports highlight a broad spectrum of the clinical phenotype. Here, we describe a novel HPCA gene variant in a pediatric patient and two affected relatives. Methods Whole exome sequencing was applied after a thorough clinical and neurological examination of the index patient and her family members. Results of neuropsychological testing were analyzed. Results Whole exome sequencing revealed a novel homozygous missense variant in the HPCA gene [c.182C>T p.(Ala61Val)] in our pediatric patient and the two affected family members. Clinically, the cases presented with dystonia, dysarthria, and jerky movements. We observed a particular cognitive profile with executive dysfunctions in our patient, which corresponds to the cognitive deficits that have been observed in the patients previously described. Conclusion We present a novel genetic variant of the HPCA gene associated with autosomal recessive dystonia in a child with childhood-onset dystonia supporting its clinical features. Furthermore, we propose specific HPCA-related cognitive changes in homozygous carriers, underlining the importance of undertaking a systematic assessment of cognition in HPCA-related dystonia.

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