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 New Possibilities in Molecular Diagnosis and Prognosis of Diseases Associated with Human Papilloma Virus in Cervical Secretion

2016 ◽  
pp. 134-139
Author(s):  
Petro Veropotvelyan ◽  
Ivan Tsehmistrenko ◽  
Mykola Veropotvelyan ◽  
Serhii Yaruchik
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Metabolic Profiles ◽  
Protein Markers ◽  
Systematic Analysis ◽  
Papilloma Virus ◽  
Diagnosis And Prognosis ◽  
Neoplastic Processes ◽  
Molecular Diagnosis And Prognosis ◽  
Cervical Secretion

The aim of the article is to determine the importance of the systematic analysis of data available in modern publications – molecular markers of cervical discharge in the diagnosis of various diseases of the cervix associated with human papilloma virus (HPV). In addition, the prospects of studying protein and metabolic profiles of cervicovaginal discharge for predicting the course of neoplastic processes of the cervix. The article describes a number of protein markers in cervical defined for the early diagnosis of precancerous diseases and cervical cancer.

Molecular Diagnosis and Prognosis in Gynecologic Oncology

1999 ◽  
Vol 123 (11) ◽  
pp. 1035-1040
Author(s):  
Steven G. Silverberg
Keyword(s):  
Molecular Pathology ◽  
Malignant Tumors ◽  
Gynecologic Oncology ◽  
Human Papillomaviruses ◽  
Diagnosis And Prognosis ◽  
Molecular Diagnosis And Prognosis ◽  
Cancer Precursors ◽  
Near Future ◽  
Female Genital

Abstract Currently, molecular pathology plays a limited role in improving patient outcome in gynecologic oncology. However, molecular investigation is providing important insights into the epidemiology, pathogenesis, and progression of female genital cancers. Future roles should include prediction of poor outcome in low-risk cases, more accurate staging of multifocal tumors, identification of new precursor lesions, and prediction of response to specific therapeutic regimens. Gene therapy of some malignant tumors may become important in the near future. In the immediate future, however, the most significant role of molecular pathology may be in the screening and triage of putative cervical cancer precursors and in the possible prophylaxis of these lesions by means of a vaccine or vaccines against human papillomaviruses.

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