Abstract
BackgroundJoubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes. There are a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 and CEP120.MethodsWe sought to explore the developmental expression patterns of ARL3 and CEP120 in humans to gain additional understanding of these genetic conditions. We used an RNA in situ detection technique called RNAscope to characterise ARL3 and CEP120 expression patterns in human embryos and foetuses in collaboration with the MRC-Wellcome Trust Human Developmental Biology Resource.ResultsBoth ARL3 and CEP120 are expressed in early human brain development, including the cerebellum and in the developing retina and kidney, consistent with the clinical phenotypes seen with pathogenic variants in these genes.ConclusionsThis study provides insights into the potential pathogenesis of JSRD by uncovering the spatial expression of two JSRD-causative genes during normal human development.
Highlights
Joubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes
This overview reveals that mutations in Centrosomal protein of 120 kDa (CEP120) are at present associated with severe phenotypes including Meckel syndrome (MKS) and that single heterozygous changes in ADP-ribosylation factor-like 3 (ARL3) are sufficient to cause retinal-limited phenotypes
ARL3 and CEP120 are expressed in early human brain development In 8PCW human brain tissue, the expression of ARL3 and CEP120 is remarkably similar
Summary
Joubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes. There are a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 and CEP120. Joubert syndrome and related disorders (JSRD) are a group of autosomal inherited ciliopathies that are characterised as a cerebello-retinal-renal phenotype, and have an incidence rate of 1:80,000–100,000 live births [1,2,3]. Due to the multi-organ involvement, varying phenotypes, and multitude of genes known to cause JSRD there is great heterogeneity within the syndrome and overlap with closely related ciliopathies including Bardet-Biedl syndrome (https://omim.org/phenotypicSeries/PS209900) and Jeune syndrome Discovered genetic causes of JSRD include ARL3 [15] and CEP120 [16, 17]; the fact that their encoded proteins have such divergent roles within the primary cilium demonstrates the complexity underlying this group of related disorders
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