Diagnostic utility of whole-genome sequencing for nephronophthisis.

Autor:	Larrue R; Service de Toxicologie et Génopathies, CHU Lille, F-59000 Lille, France.; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020- UMR-S 1277, F-59000 Lille, France., Chamley P; Service de Néphrologie, CHU Lille, F-59000 Lille, France., Bardyn T; Service de Toxicologie et Génopathies, CHU Lille, F-59000 Lille, France., Lionet A; Service de Néphrologie, CHU Lille, F-59000 Lille, France., Gnemmi V; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020- UMR-S 1277, F-59000 Lille, France.; Service d'Anatomo-pathologie, CHU Lille, F-59000 Lille, France., Cauffiez C; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020- UMR-S 1277, F-59000 Lille, France., Glowacki F; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020- UMR-S 1277, F-59000 Lille, France.; Service de Néphrologie, CHU Lille, F-59000 Lille, France., Pottier N; Service de Toxicologie et Génopathies, CHU Lille, F-59000 Lille, France.; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020- UMR-S 1277, F-59000 Lille, France., Broly F; Service de Toxicologie et Génopathies, CHU Lille, F-59000 Lille, France.
Jazyk:	angličtina
Zdroj:	NPJ genomic medicine [NPJ Genom Med] 2020 Sep 21; Vol. 5, pp. 38. Date of Electronic Publication: 2020 Sep 21 (Print Publication: 2020).
DOI:	10.1038/s41525-020-00147-8
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing interests. (© The Author(s) 2020.)
Databáze:	MEDLINE
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