scholarly journals Stickler syndrome – lessons from a national cohort

Eye ◽  
2021 ◽  
Author(s):  
M. P. Snead ◽  
A. J. Richards ◽  
A. M. McNinch ◽  
P. Alexander ◽  
H. Martin ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Molecular Genetic ◽  
Risk Groups ◽  
Genetic Mutation ◽  
Molecular Genetic Analysis ◽  
Stickler Syndrome ◽  
Common Cause ◽  
Giant Retinal Tear ◽  
National Cohort ◽  
Learning Points

AbstractIn 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.

scholarly journals Therapeutic and diagnostic advances in Stickler syndrome

2020 ◽  
Vol 1 ◽  
pp. 263300402097866
Author(s):  
Martin Snead ◽  
Howard Martin ◽  
Peter Bale ◽  
Nick Shenker ◽  
David Baguley ◽  
...  
Keyword(s):  
High Risk ◽  
Retinal Detachment ◽  
Connective Tissue ◽  
Individual Risk ◽  
Stickler Syndrome ◽  
Plain Language ◽  
Connective Tissue Disorders ◽  
Specialist Service ◽  
Common Cause ◽  
Systemic Involvement

The Stickler syndromes are the leading cause of inherited retinal detachment and the most common cause of rhegmatogenous retinal detachment in childhood. The clinical and molecular genetic spectrum of this connective tissue disorder is discussed in this article, emphasising the key role the ophthalmologist has to play in the identification, diagnosis and prevention of blindness in the increasingly widely recognised sub-groups with ocular-only (or minimal systemic) involvement. Without diagnosis and prophylaxis in such high-risk subgroups, these patients are at high risk of Giant Retinal Tear detachment and blindness, especially in the paediatric population, where late or second eye involvement is common. Initially considered a monogenic disorder, there are now known to be at least 11 distinct phenotypic subgroups in addition to allied connective tissue disorders that can present to the clinician as part of the differential diagnosis. Plain language summary Treatment and diagnostic advances in Stickler syndrome The Stickler syndromes are a group of related connective tissue disorders that are associated with short-sight and a very high risk of blindness from detachment of the retina – the light sensitive film at the back of the eye. Other features include cleft palate, deafness and premature arthritis. It is the most common cause of retinal detachment in children and the most common cause of familial or inherited retinal detachment. In contrast to most other forms of blinding genetic eye disease, blindness from retinal detachment in Stickler syndrome is largely avoidable with accurate diagnosis and prophylactic (preventive) surgery. Recent advances in the understanding of the genetic causes of Stickler syndrome mean that the diagnosis can now be confirmed in over 95% of cases and, most importantly, the patient’s individual risk of retinal detachment can be graded. Preventative surgery is hugely effective in reducing the incidence of retinal detachment in those patients shown to be at high risk. NHS England have led the way in the multidisciplinary care for patients with Stickler syndrome by launching a highly specialist service that has been free at point of care to all NHS patients in England since 2011 ( https://www.england.nhs.uk/commissioning/spec-services/highly-spec-services , www.vitreoretinalservice.org )

scholarly journals Role of AGTR1 A/C polymorphism in the development of atrial fibrillation

2017 ◽  
Vol 89 (9) ◽  
pp. 48-52
Author(s):  
A V Kuskaeva ◽  
S Yu Nikulina ◽  
A A Chernova ◽  
N V Aksyutina ◽  
A P Kuskaev ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Genetic ◽  
Geographical Location ◽  
Risk Groups ◽  
Molecular Genetic Analysis ◽  
Climatic Conditions ◽  
Control Group ◽  
Study Group ◽  
Genetic Features ◽  
Electrocardiogram Monitoring

Aim. To investigate the AGTR1 A/C polymorphism associated with atrial fibrillation (AF) to form risk groups among patients who are prone to this disease. Subjects and methods. 90 probands with a confirmed diagnosis of AF and their 144 first-, second-, and third-degree relatives were examined. These families made up a study group. A control group was formed of 100 apparently healthy individuals without a history of cardiovascular diseases. Collection of medical history data and complaints, electrocardiography, electrocardiogram monitoring, as well as molecular genetic analysis, thyroid hormone tests were done in all the patients. Results. No statistically significant data on the correlation between the AGTR1 A/C polymorphism and the development of AF were obtained in any patient subgroup. The obtained results can be due to the genetic features of a Siberian population, which are dependent on climatic conditions and geographical location, and confirm that AF is a heterogeneous disease. Conclusion. There were no statistically significant differences between the patients in the study group and those in the control group. Our findings suggest the heterogeneity of AF and confirm its multifactorial nature.

Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

2013 ◽  
Vol 20 (1-2) ◽  
pp. 1-8
Author(s):  
MM Rahman ◽  
L Rahman ◽  
SN Begum ◽  
F Nur
Keyword(s):  
Genetic Distance ◽  
Gene Diversity ◽  
Random Amplified Polymorphic Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polymorphic Loci ◽  
Rice Genotypes ◽  
High Level ◽  
Genetic Diversity Study ◽  
Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Nei’s genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 – 8, 2009

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

scholarly journals MOLECULAR GENETIC ANALYSIS OF THE DILUTE-SHORT EAR (d-se) REGION OF THE MOUSE

Genetics ◽  
1986 ◽  
Vol 112 (2) ◽  
pp. 321-342
Author(s):  
Eugene M Rinchik ◽  
Liane B Russell ◽  
Neal G Copeland ◽  
Nancy A Jenkins
Keyword(s):  
Physical Map ◽  
Leukemia Virus ◽  
Molecular Genetic ◽  
Break Point ◽  
Virus Genome ◽  
Molecular Genetic Analysis ◽  
Chromosome 9 ◽  
Genetic Complementation ◽  
Induced Mutations ◽  
Radiation Induced

ABSTRACT Genes of the dilute-short ear (d-se) region of mouse chromosome 9 comprise an array of loci important to the normal development of the animal. Over 200 spontaneous, chemically induced and radiation-induced mutations at these loci have been identified, making it one of the most genetically well-characterized regions of the mouse. Molecular analysis of this region has recently become feasible by the identification of a dilute mutation that was induced by integration of an ecotropic murine leukemia virus genome. Several unique sequence cellular DNA probes flanking this provirus have now been identified and used to investigate the organization of wild-type chromosomes and chromosomes with radiation-induced d-se region mutations. As expected, several of these mutations are associated with deletions, and, in general, the molecular and genetic complementation maps of these mutants are concordant. Furthermore, a deletion break-point fusion fragment has been identified and has been used to orient the physical map of the d-se region with respect to the genetic complementation map. These experiments provide important initial steps for analyzing this developmentally important region at the molecular level, as well as for studying in detail how a diverse group of mutagens acts on the mammalian germline.

scholarly journals Repeated molecular genetic analysis in Brugada syndrome revealed a novel disease-associated large deletion in the SCN5A gene

2016 ◽  
Vol 2 (3) ◽  
pp. 261-264 ◽  
Author(s):  
Anders Krogh Broendberg ◽  
Lisbeth Noerum Pedersen ◽  
Jens Cosedis Nielsen ◽  
Henrik Kjaerulf Jensen
Keyword(s):  
Genetic Analysis ◽  
Brugada Syndrome ◽  
Molecular Genetic ◽  
Large Deletion ◽  
Molecular Genetic Analysis ◽  
Scn5a Gene

scholarly journals Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia

2021 ◽  
Vol 22 (15) ◽  
pp. 7842
Author(s):  
Susanne Kohl ◽  
Britta Baumann ◽  
Francesca Dassie ◽  
Anja K. Mayer ◽  
Maria Solaki ◽  
...  
Keyword(s):  
Segregation Analysis ◽  
Molecular Genetic ◽  
Retinal Disease ◽  
Underlying Mechanism ◽  
Recurrence Risk ◽  
Molecular Genetic Analysis ◽  
Recessive Mutation ◽  
Chromosome 2 ◽  
Inherited Retinal Disease ◽  
Uniparental Isodisomy

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.

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