Abstract
Nephronophthisis-related ciliopathies (NPHP-RC) are a group of inherited genetic disorders that share a defect in the formation, maintenance or functioning of the primary cilium complex, causing progressive cystic kidney disease and other clinical manifestations. Mutations in centrosomal protein 164 kDa (CEP164), also known as NPHP15, have been identified as a cause of NPHP-RC. Here we have utilised the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) to perform immunohistochemistry studies on human embryonic and foetal tissues to determine the expression patterns of CEP164 during development. Notably expression is widespread, yet defined, in multiple organs including the kidney, retina and cerebellum. Murine studies demonstrated an almost identical Cep164 expression pattern. Taken together, these data support a conserved role for CEP164 throughout the development of numerous organs, which, we suggest, accounts for the multi-system disease phenotype of CEP164-mediated NPHP-RC.
Highlights
Nephronophthisis-related ciliopathies (NPHP-renal corpuscle (RC)) are a collection of inherited genetic disorders, grouped together by a core defect in the formation, maintenance or functioning of the primary cilium complex [1, 2]
In this study we have described the expression of centrosomal protein 164 kDa (CEP164) in the developing human embryo and foetus, utilising immunohistochemistry, focusing upon the kidney, retina and cerebellum
Primary cilia are vital in the kidney for mechanosensation and chemical signal transduction, which is required for orientated cellular divisions during development and kidney maintenance
Summary
Nephronophthisis-related ciliopathies (NPHP-RC) are a collection of inherited genetic disorders, grouped together by a core defect in the formation, maintenance or functioning of the primary cilium complex [1, 2]. NPHP-RC patients typically present with nephronophthisis, a fibrotic cortico-medullary cystic kidney phenotype, which frequently leads to end stage-renal disease (ESRD) [3, 4]. In some NPHP-RC cases, including Senior-Løken syndrome (SLSN), Alstrom syndrome (AS), Bardet Biedl syndrome (BBS) and Joubert syndrome (JBTS), patients have retinal dysplasia and degeneration phenotypes, such as Leber congenital amaurosis, which can deteriorate to blindness [5,6,7]. Neurological abnormalities are often present; JBTS patients have midbrain cerebellar vermis hypoplasia, characterised by the “molar tooth” sign on MRI analysis [5, 8], leading to numerous problems including ataxia, hypotonia and breathing abnormalities.
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