Molecular diagnosis and prognosis with DNA microarrays

Hematology ◽  
2011 ◽  
Vol 16 (3) ◽  
pp. 166-176
Author(s):  
Marco Wiltgen ◽  
Gernot P Tilz
Keyword(s):  
Molecular Diagnosis ◽  
Dna Microarrays ◽  
Diagnosis And Prognosis ◽  
Molecular Diagnosis And Prognosis

scholarly journals Neonatal-onset mitochondrial disease: clinical features, molecular diagnosis and prognosis

2021 ◽  
pp. fetalneonatal-2021-321633
Author(s):  
Tomohiro Ebihara ◽  
Taro Nagatomo ◽  
Yohei Sugiyama ◽  
Tomoko Tsuruoka ◽  
Yoshiteru Osone ◽  
...  
Keyword(s):  
Clinical Features ◽  
Molecular Diagnosis ◽  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Leigh Syndrome ◽  
Diagnosis And Prognosis ◽  
Neonatal Onset ◽  
Initial Symptoms ◽  
Dna Variants ◽  
Molecular Diagnosis And Prognosis

ObjectiveNeonatal-onset mitochondrial disease has not been fully characterised owing to its heterogeneity. We analysed neonatal-onset mitochondrial disease in Japan to clarify its clinical features, molecular diagnosis and prognosis.DesignRetrospective observational study from January 2004 to March 2020.SettingPopulation based.PatientsPatients (281) with neonatal-onset mitochondrial disease diagnosed by biochemical and genetic approaches.InterventionsNone.Main outcome measuresDisease types, initial symptoms, biochemical findings, molecular diagnosis and prognosis.ResultsOf the 281 patients, multisystem mitochondrial disease was found in 194, Leigh syndrome in 26, cardiomyopathy in 38 and hepatopathy in 23 patients. Of the 321 initial symptoms, 236 occurred within 2 days of birth. Using biochemical approaches, 182 patients were diagnosed by mitochondrial respiratory chain enzyme activity rate and 89 by oxygen consumption rate. The remaining 10 patients were diagnosed using a genetic approach. Genetic analysis revealed 69 patients had nuclear DNA variants in 36 genes, 11 of 15 patients had mitochondrial DNA variants in five genes and four patients had single large deletion. The Cox proportional hazards regression analysis showed the effects of Leigh syndrome (HR=0.15, 95% CI 0.04 to 0.63, p=0.010) and molecular diagnosis (HR=1.87, 95% CI 1.18 to 2.96, p=0.008) on survival.ConclusionsNeonatal-onset mitochondrial disease has a heterogenous aetiology. The number of diagnoses can be increased, and clarity regarding prognosis can be achieved by comprehensive biochemical and molecular analyses using appropriate tissue samples.

scholarly journals Diagnostic utility of whole-genome sequencing for nephronophthisis

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Romain Larrue ◽  
Paul Chamley ◽  
Thomas Bardyn ◽  
Arnaud Lionet ◽  
Viviane Gnemmi ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Molecular Diagnosis ◽  
Kidney Diseases ◽  
Single Gene ◽  
Whole Genome ◽  
Autosomal Recessive Disorders ◽  
Monogenic Disorders ◽  
Diagnosis And Prognosis ◽  
End Stage

Abstract Next-generation sequencing has revolutionized the molecular diagnosis of individuals affected by genetic kidney diseases. Indeed, rapid genetic testing in individuals with suspected inherited nephropathy has not only important implications for diagnosis and prognosis but also for genetic counseling. Nephronophthisis (NPHP) and related syndromes, a leading cause of end-stage renal failure, are autosomal recessive disorders characterized by the variable presentation and considerable locus heterogeneity with more than 90 genes described as single-gene causes. In this case report, we demonstrate the utility of whole-genome sequencing (WGS) for the molecular diagnosis of NPHP by identifying two putative disease-causing intronic mutations in the NPHP3 gene, including one deep intronic variant. We further show that both intronic variants, by affecting splicing, result in a truncated nephrocystin-3 protein. This study provides a framework for applying WGS as a first-line diagnostic tool for highly heterogeneous disease such as NPHP and further suggests that deep intronic variations are an important underestimated cause of monogenic disorders.

scholarly journals Use of High-Throughput DNA Microarrays to Identify Biomarkers for Bladder Cancer

2003 ◽  
Vol 49 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Marta Sánchez-Carbayo
Keyword(s):  
Bladder Cancer ◽  
Clinical Outcome ◽  
High Throughput ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tumor Stage ◽  
Ease Of Use ◽  
Tumor Subtypes ◽  
Diagnosis And Prognosis

Abstract Background: Numerous markers have been described to correlate to some extent with tumor stage and prognosis of patients with bladder cancer. The power of many of these biomarkers in detecting superficial disease or predicting the clinical outcome of individual tumors is limited, and alternative markers are still in demand. High-throughput microarrays represent novel means for cancer research and tumor marker discovery. Approach: The aim of this report was to discuss the application of DNA technologies to provide novel biomarkers for bladder cancer. Content: Specific bladder tumor subtypes have distinct gene expression profiles. The use of high-throughput DNA microarrays allows identification of the most prevalent and relevant alterations within bladder tumors. Clusters of differentially expressed genes will become biomarkers to discriminate subgroups of patients with different histopathology or clinical outcome. Additionally, the identified individual molecular targets might be further validated and developed into novel serum or urinary biomarkers for the diagnosis and/or as prognostic factors to be applied in clinical practice. The diagnosis and prognosis of bladder cancer would be enhanced by the use of such markers, and the marker itself may constitute a therapeutic target when studied in appropriate patients and control groups. Summary: Expression profiling with high-throughput DNA microarrays has the potential of providing critical clues for the management of bladder cancer patients. As the quality, standardization, and ease of use of the technology increase and the costs decrease, DNA microarrays will move from being a technology restricted to research to clinical laboratories in the near future.

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