Affiliations: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK
Note:  Corresponding author: John A. Sayer, MB ChB, FRCP, PhD, Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK. Tel.: +44 1912418608; Fax: +44 191241866; E-mail: [email protected]
Abstract: Nephronophthisis (NPHP) is a childhood cystic kidney disease, which almost invariably leads to end-stage renal disease in those affected. Recognition and diagnosis requires clinical suspicion, biochemical evaluation, renal imaging and historically, renal biopsy. Modern molecular genetics now allows a diagnosis to be made in a significant proportion of cases. Mutations in NPHP1 account for 20% of cases, but the disease is genetically heterogeneous with at least 20 different genes associated with NPHP. Recent developments in the fields of genetics and proteomics have led to increased understanding of the underlying pathogenetic defects. Almost all NPHP genes encode proteins, which localize to the primary cilia, basal body and centrosome. NPHP is a therefore considered to be a ciliopathy, and can be part of a broad spectrum of clinical disease that includes extra-renal manifestations including retinal degeneration, cerebellar ataxia, liver fibrosis and situs inversus. In this review, we discuss the historical descriptions of NPHP in the context of more recent developments in our understanding of this disease.