Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past, present and future

Abstract Background and Aims Bardet Biedl Syndrome (BBS) is a rare genetic disorder characterized by a wide range of organ dysfunction, including kidney disease. The severity of renal dysfunction is highly variable in this setting, ranging from tubular defects to the end stage renal disease, with poor genotype-phenotype correlation. Proteomics and metabolomics are powerful tools able to contribute to the better understanding of molecular basis of disease conditions. Our previous studies demonstrated that the urinary proteomic pattern of BBS patients differed from that of healthy subjects, with a set of deregulated proteins including cell adhesion and extracellular matrix organization proteins (1). The present study aims to characterize urine metabolomic profile of BBS patients, in order to identify both 1) potential disease biomarkers and 2) aberrant metabolic pathways underlying renal disease Method To this end, in the pilot study urine samples have been collected from 14 adult BBS patients and have been compared with healthy volunteers, using an untargeted strategy. In the confirmation study, 24 BBS patients with wide range of kidney dysfunction have been enrolled, and additional control groups, besides healthy subjects, were included: 1) age-gender-matched chronic kidney disease patients by other causes and 2) obese individuals. Results Several metabolites were de-regulated in BBS patients compared with normal subjects (lactic acid, glycolic acid,3-Hydroxypropionic acid, pyruvic acid, 3-hydroxyisobutyric acid, 2-ethyl-3-hydroxy-propionic acid, succinic acid, fumaric acid, erythropentonic acid, 2-hydroxyglutaric acid, 4-hydroxyphenyllactic acid, 3,4-pyridinedicarboxylic acid, retinoic acid, 4-hydroxyphenylacetic acid, palmitic acid, 9-Hexadecenoic acid, oleic acid and 9-Octadecenoic acid). The clusterization performed by MetaboAnalyst tool, revealed a possible deregulation of different metabolic pathways, including glycolysis, TCA cycle, pyruvate metabolism, lipids biosynthesis and glutamate metabolism (p-value <0.01) (figure 1); some of these pathways were described as de-regulated in other ciliopathies (2). In the confirmation study (on-going studies) some metabolites, including lactic acid and intermediates of Krebs cycle, correlated with kidney dysfunction only in the BBS group. Conclusion These findings suggest that urine metabolomic fingerprint of BBS patients is different from that of healthy subjects and indicate a possible deregulation of several metabolic pathways; some urinary molecules correlated with kidney dysfunction only in BBS patients, suggesting the specificity of these results.

Download Full-text

Mutation profile of BBS genes in patients with Bardet–Biedl syndrome: an Italian study

Italian Journal of Pediatrics ◽

10.1186/s13052-019-0659-1 ◽

2019 ◽

Vol 45 (1) ◽

Cited By ~ 7

Author(s):

Elena Manara ◽

Stefano Paolacci ◽

Fabiana D’Esposito ◽

Andi Abeshi ◽

Lucia Ziccardi ◽

...

Keyword(s):

Bardet Biedl Syndrome ◽

Italian Study ◽

Mutation Profile

Download Full-text

Bardet–Biedl syndrome 1 genotype and obesity in the Newfoundland population

International Journal of Obesity ◽

10.1038/sj.ijo.0802601 ◽

2004 ◽

Vol 28 (5) ◽

pp. 680-684 ◽

Cited By ~ 16

Author(s):

Y Fan ◽

P Rahman ◽

L Peddle ◽

D Hefferton ◽

N Gladney ◽

...

Keyword(s):

Bardet Biedl Syndrome

Download Full-text

The Laurence-Moon-Bardet-Biedl Syndrome: Unresponsiveness to the Action of Testosterone, A Possible Mechanism**Presented in part at the Sixth Asia and Oceania Congress of Endocrinology, January 22 to 27, 1978, Singapore.

Fertility and Sterility ◽

10.1016/s0015-0282(16)43940-3 ◽

1979 ◽

Vol 31 (4) ◽

pp. 417-422 ◽

Cited By ~ 6

Author(s):

Gholamali Mozaffarian ◽

Manuchehr K. Nakhjavani ◽

Abdolreza Farrahi

Keyword(s):

Bardet Biedl Syndrome

Download Full-text