3 research outputs found
The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies
Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease
Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children
International audienceMultiorgan sequelae of coronavirus disease 2019 (COVID-19) beyond the acute phase of infection are increasingly described as clinical experience expands. In children, acute COVID-19 appears to be generally asymptomatic or mild. Yet, the multisystem inflammatory syndrome in children (MIS-C) may be a severe postinfectious complication following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 During the first pandemic year, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. Causes of aTIN include drugs, infections, and systemic diseases, but often remain undetermined. The rare TINUs syndrome associating aTIN and uveitis is considered to result from a still ill-characterized immune-mediated process. The observed increased incidence of idiopathic aTIN/TINUs prompted us to examine whether SARS-CoV-2 might be the initial trigger