Somatic mutation in autosomal dominant polycystic kidney disease revealed by deep sequencing human kidney cysts.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) results in progressive cysts that lead to kidney failure, and is caused by heterozygous germline variants in PKD1 or PKD2. Cyst pathogenesis is not definitively understood. Somatic second-hit mutations have been implicated in cyst pathogenesis, though technical sequencing challenges have limited investigation.

Mechanisms that potentially contribute to the development of post-streptococcal glomerulonephritis.

Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens).

Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation.

Purpose: To assess the relative cost-effectiveness of genomic testing compared with standard non-genomic diagnostic investigations in patients with suspected monogenic kidney disease from an Australian health care system perspective.

Methods: Diagnostic and clinical information was used from a national cohort of 349 participants. Simulation modelling captured diagnostic, health, and economic outcomes during a time horizon from clinical presentation until 3 months post-test results based on the outcome of cost per additional diagnosis and lifetime horizon based on cost per quality-adjusted life-year (QALY) gained.

Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Background And Objectives: Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, and causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive genetic diagnostic test would be highly useful and transform the field.

Genomic diagnostics in polycystic kidney disease: an assessment of real-world use of whole-genome sequencing.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is common, with a prevalence of 1/1000 and predominantly caused by disease-causing variants in PKD1 or PKD2. Clinical diagnosis is usually by age-dependent imaging criteria, which is challenging in patients with atypical clinical features, without family history, or younger age. However, there is increasing need for definitive diagnosis of ADPKD with new treatments available.

Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease.

Monoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype.

Increased Diagnostic Yield of Spastic Paraplegia with or Without Cerebellar Ataxia Through Whole-Genome Sequencing.

Inherited disorders of spasticity or ataxia exist on a spectrum with overlapping causative genes and phenotypes. We investigated the use of whole-genome sequencing (WGS) to detect a genetic cause when considering this spectrum of disorders as a single group. We recruited 18 Korean individuals with spastic paraplegia with or without cerebellar ataxia in whom common causes of hereditary cerebellar ataxia and hereditary spastic paraplegia had been excluded.

Population data improves variant interpretation in autosomal dominant polycystic kidney disease.

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is a common adult-onset monogenic disorder, with prevalence of 1/1000. Population databases including ExAC have improved pathogenic variant prioritization in many diseases. Due to pseudogene homology of PKD1, the predominant ADPKD disease gene, and the variable disease severity and age of onset, we aimed to investigate the utility of ExAC for variant assessment in ADPKD.

Expanding the spectrum of mutations and novel insights into disease mechanisms.

Zellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different genes. This includes , an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in [NM_004813.

Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder and is due to disease-causing variants in PKD1 or PKD2. Strong genotype-phenotype correlation exists although diagnostic sequencing is not part of routine clinical practice. This is because PKD1 bears 97.