Mutation screening of 17 candidate genes in a cohort of 67 probands with early‐onset high myopia

2020 ◽  
Vol 40 (3) ◽  
pp. 271-280 ◽  
Author(s):  
Fang Liu ◽  
Junwen Wang ◽  
Yiqiao Xing ◽  
Tuo Li
Keyword(s):  
Candidate Genes ◽  
Early Onset ◽  
High Myopia ◽  
Mutation Screening

scholarly journals Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Noémi Széll ◽  
Tamás Fehér ◽  
Zoltán Maróti ◽  
Tibor Kalmár ◽  
Dóra Latinovics ◽  
...  
Keyword(s):  
Middle Ages ◽  
Early Onset ◽  
Colour Vision ◽  
High Myopia ◽  
Field Testing ◽  
Cone Dystrophy ◽  
Ophthalmological Examination ◽  
Whole Exome ◽  
Caucasian Family ◽  
Cone System

Abstract Background Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis. Results We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

scholarly journals Bilateral Sturge-Weber syndrome presenting with early onset convulsion and high myopia

2015 ◽  
Vol 8 (1) ◽  
pp. 78
Author(s):  
Sabyasachi Bandyopadhyay ◽  
Indrani Bhattacharjee ◽  
SanatKumar Ghosh ◽  
KanchanKumar Mondal
Keyword(s):  
Early Onset ◽  
High Myopia ◽  
Weber Syndrome ◽  
Sturge Weber Syndrome

Association Studies of Serotonin System Candidate Genes in Early-onset Obsessive-Compulsive Disorder

2007 ◽  
Vol 61 (3) ◽  
pp. 322-329 ◽  
Author(s):  
Diane E. Dickel ◽  
Jeremy Veenstra-VanderWeele ◽  
Nancy Chiu Bivens ◽  
Xiaolin Wu ◽  
Daniel J. Fischer ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Obsessive Compulsive Disorder ◽  
Early Onset ◽  
Association Studies ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Serotonin System

Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism

2016 ◽  
Vol 124 (4) ◽  
pp. 431-435 ◽  
Author(s):  
Chikara Yamashita ◽  
Manabu Funayama ◽  
Yuanzhe Li ◽  
Hiroyo Yoshino ◽  
Hitoshi Yamada ◽  
...  
Keyword(s):  
Early Onset ◽  
Mutation Screening ◽  
Japanese Patients

scholarly journals The Missing Heritability of Sporadic Frontotemporal Dementia: New Insights from Rare Variants in Neurodegenerative Candidate Genes

2019 ◽  
Vol 20 (16) ◽  
pp. 3903 ◽  
Author(s):  
Miriam Ciani ◽  
Cristian Bonvicini ◽  
Catia Scassellati ◽  
Matteo Carrara ◽  
Carlo Maj ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Frontotemporal Dementia ◽  
Candidate Genes ◽  
Early Onset ◽  
Genetic Factors ◽  
Rare Variants ◽  
Late Onset ◽  
Genetic Effect ◽  
Lewy Body Dementia ◽  
Missing Heritability

Frontotemporal dementia (FTD) is a common form of dementia among early-onset cases. Several genetic factors for FTD have been revealed, but a large proportion of FTD cases still have an unidentified genetic origin. Recent studies highlighted common pathobiological mechanisms among neurodegenerative diseases. In the present study, we investigated a panel of candidate genes, previously described to be associated with FTD and/or other neurodegenerative diseases by targeted next generation sequencing (NGS). We focused our study on sporadic FTD (sFTD), devoid of disease-causing mutations in GRN, MAPT and C9orf72. Since genetic factors have a substantially higher pathogenetic contribution in early onset patients than in late onset dementia, we selected patients with early onset (<65 years). Our study revealed that, in 50% of patients, rare missense potentially pathogenetic variants in genes previously associated with Alzheimer’s disease, Parkinson disease, amyotrophic lateral sclerosis and Lewy body dementia (GBA, ABCA7, PARK7, FUS, SORL1, LRRK2, ALS2), confirming genetic pleiotropy in neurodegeneration. In parallel, a synergic genetic effect on FTD is suggested by the presence of variants in five different genes in one single patient. Further studies employing genome-wide approaches might highlight pathogenic variants in novel genes that explain the still missing heritability of FTD.

Abstract 2787: Exon sequencing of candidate genes for early onset ER negative breast cancer risk reveals novel gene-level associations

2015 ◽  
Author(s):  
Molly Scannell Bryan ◽  
Muhammad G. Kibirya ◽  
Irene Andrulis ◽  
Jenny Chang-Claude ◽  
Habibul Ahsan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Candidate Genes ◽  
Early Onset ◽  
Novel Gene ◽  
Gene Level

Sequencing candidate genes in African American and Hispanic/ Latino probands with early-onset Atrial Fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Chalazan ◽  
D Mol ◽  
A Sridhar ◽  
A Ornelas-Loredo ◽  
F Darbar ◽  
...  
Keyword(s):  
African American ◽  
Candidate Genes ◽  
Ethnic Minorities ◽  
Early Onset ◽  
Heart Association ◽  
Read Depth ◽  
Funding Source ◽  
Loss Of Function ◽  
Hispanic Latinos ◽  
Family Based

Abstract Introduction Mutations in cardiac ion channels, structural proteins and signaling molecules have been identified in European whites with early-onset AF (EOAF). However, it remains unclear if genetic variation also contributes to the etiology of EOAF in ethnic minorities. Purpose To determine the prevalence of disease causing variants in candidate AF genes in African American and Hispanic/Latino probands with EOAF. Method In this family-based study, probands of African and Hispanic descent with EOAF (defined as AF ≤65 years) were prospectively enrolled in a clinical-DNA biorepository and underwent targeted sequencing for 60 AF candidate genes. Variants were filtered at 20X read depth and clinically evaluated with American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) as well as the Association for Clinical Genomic Science (ACGS) criteria for disease-causing mutations. Results Among 227 EOAF probands with mean (SD) age of AF 51.0 (9.9) years, 132 (58.0%) were men and 148 (65.0%) African American and 79 (35.0%) Hispanic/Latino. Sequencing 60 candidate AF genes revealed 90 variants that met filtering criteria and underwent clinical evaluation. We identified 16 (7.0%) EOAF probands with a likely pathogenic or pathogenic variant with the majority being loss of function (62.5%) and located in the TTN gene (50.0%). We confirmed a family history of AF in 24 probands (10.6%) and 6 families with &gt;1 affected member a variant of unknown significance (VUS) in genes encoding for a sodium channel (SCN10A), potassium channel (KCNE5), sarcomeric proteins (MYH6, TTN) and atrial natriuretic peptide (NPPA) co-segregated with AF. Conclusion Gene sequencing in African American and Hispanic/Latinos probands with EOAF identified a small percentage of disease causing variants in patients with EOAF. Our findings not only represent important progress toward molecular phenotyping of EOAF, but also provides insight into the underlying pathophysiology toward targeted mechanism-based therapies for AF in ethnic minorities. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): American Heart Association

scholarly journals Exome sequencing study of 20 patients with high myopia

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5552 ◽  
Author(s):  
Ling Wan ◽  
Boling Deng ◽  
Zhengzheng Wu ◽  
Xiaoming Chen
Keyword(s):  
Exome Sequencing ◽  
Candidate Genes ◽  
High Myopia ◽  
Cellular Response ◽  
Gene Mutations ◽  
Enrichment Analysis ◽  
Zinc Ion ◽  
Ocular Disease ◽  
Disease Genes ◽  
Bioinformatics Analyses

Background High myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing (WES) study to identify potential causal gene mutations. Methods A total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes. Results In 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. A total of 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in five known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in seven ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation. Discussion Systematic mutation analysis of candidate genes was performed using WES data, functional interaction (FI) network, Gene Ontology and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.

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