Proteomic and Transcriptomic Landscapes of Alstrom and Bardet-Biedl Syndromes

Alstrom syndrome (ALMS) and Bardet-Biedl syndrome (BBS) are rare genetic diseases with a number of common clinical features ranging from early-childhood obesity and retinal degeneration. ALMS and BBS belong to the ciliopathies, which are known to have the expression products of genes, encoding them as cilia-localized proteins in multiple target organs. The aim of this study was to perform transcriptomic and proteomic analysis on cellular models of ALMS and BBS syndromes to identify common and distinct pathological mechanisms present in both syndromes. For this purpose, epithelial cells were isolated from the urine of patients and healthy subjects, which were then cultured and reprogrammed into induced pluripotent stem (iPS) cells. The pathways of genes associated with the metabolism of lipids and glycosaminoglycan and the transport of small molecules were found to be concomitantly downregulated in both diseases, while transcripts related to signal transduction, the immune system, cell cycle control and DNA replication and repair were upregulated. Furthermore, protein pathways associated with autophagy, apoptosis, cilium assembly and Gli1 protein were upregulated in both ciliopathies. These results provide new insights into the common and divergent pathogenic pathways between two similar genetic syndromes, particularly in relation to primary cilium function and abnormalities in cell differentiation.

Automated summary

This study conducted transcriptomic and proteomic analysis on cellular models of Alstrom syndrome and Bardet-Biedl syndrome, identifying common and distinct pathological mechanisms between the two syndromes. Genes related to lipid and glycosaminoglycan metabolism and small molecule transport were downregulated, while those associated with signal transduction, immune system, cell cycle control, and DNA replication and repair were upregulated. Protein pathways involved in autophagy, apoptosis, cilium assembly, and Gli1 protein were also upregulated in both syndromes.