Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;101(4):429-441.
doi: 10.1111/cge.14119.

Kidney failure in Bardet-Biedl syndrome

Jennifer R Meyer  1 , Anthony D Krentz  2 , Richard L Berg  3 , Jesse G Richardson  3 , Jeremy Pomeroy  4 , Scott J Hebbring  5 , Robert M Haws  4   6
Affiliations

Kidney failure in Bardet-Biedl syndrome

Jennifer R Meyer et al. Clin Genet. 2022 Apr.

Abstract

The aim of this study was to explore kidney failure (KF) in Bardet-Biedl syndrome (BBS), focusing on high-risk gene variants, demographics, and morbidity. We employed the Clinical Registry Investigating BBS (CRIBBS) to identify 44 (7.2%) individuals with KF out of 607 subjects. Molecularly confirmed BBS was identified in 37 KF subjects and 364 CRIBBS registrants. KF was concomitant with recessive causal variants in 12 genes, with BBS10 the most predominant causal gene (26.6%), while disease penetrance was highest in SDCCAG8 (100%). Two truncating variants were present in 67.6% of KF cases. KF incidence was increased in genes not belonging to the BBSome or chaperonin-like genes (p < 0.001), including TTC21B, a new candidate BBS gene. Median age of KF was 12.5 years, with the vast majority of KF occurring by 30 years (86.3%). Females were disproportionately affected (77.3%). Diverse uropathies were identified, but were not more common in the KF group (p = 0.672). Kidney failure was evident in 11 of 15 (73.3%) deaths outside infancy. We conclude that KF poses a significant risk for premature morbidity in BBS. Risk factors for KF include female sex, truncating variants, and genes other than BBSome/chaperonin-like genes highlighting the value of comprehensive genetic investigation.

Trial registration: ClinicalTrials.gov NCT03013543 NCT03651765.

Keywords: Bardet-Biedl syndrome; chronic kidney disease; ciliopathies; genetic association studies; urogenital abnormalities.

PubMed Disclaimer

Conflict of interest statement

RH is a consultant for Rhythm Pharmaceuticals and Axovia Therapeutics, LLC and principal investigator for the Setmelanotide Phase 2 Treatment Trial in Patients with Rare Genetic Obesity (ClinicalTrials.gov NCT03013543) and Long Term Extension Trial of Setmelanotide (Clinical Trials.gov NCT03651765) sponsored by Rhythm Pharmaceuticals. JP receives research funding from Rhythm Pharmaceuticals and Axovia Therapeutics. SH received research funding from Rhythm Pharmaceuticals. All other authors report no conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Kidney failure (KF) prevalence by age and sex; (B) All‐cause mortality risk in KF population
FIGURE 2
FIGURE 2
Gene frequency in kidney failure (KF) cohort compared with all CRIBBS participants [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Distribution of CRIBBS participants with molecular diagnosis by (A) gene variant and (B) gene group [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Kidney failure (KF) incidence by age and protein group
See this image and copyright information in PMC

References

    1. O'Dea D, Parfrey PS, Harnett JD, Hefferton D, Cramer BC, Green J. The importance of renal impairment in the natural history of Bardet–Biedl syndrome. Am J Kidney Dis. 1996;27(6):776‐783. doi:10.1016/s0272-6386(96)90513-2 - DOI - PubMed
    1. Florea L, Caba L, Gorduza EV. Bardet–Biedl syndrome‐multiple kaleidoscope images: insight into mechanisms of genotype‐phenotype correlations. Genes. 2021;12(9):1353. doi:10.3390/genes12091353 - DOI - PMC - PubMed
    1. Shamseldin HE, Shaheen R, Ewida N, et al. The morbid genome of ciliopathies: an update. Genet Med. 2020;22(6):1051‐1060. doi:10.1038/s41436-020-0761-1 - DOI - PubMed
    1. Lindstrand A, Frangakis S, Carvalho CM, et al. Copy‐number variation contributes to the mutational load of Bardet–Biedl syndrome. Am J Hum Genet. 2016;99(2):318‐336. doi:10.1016/j.ajhg.2015.04.023 - DOI - PMC - PubMed
    1. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364(16):1533‐1543. doi:10.1056/NEJMra1010172 - DOI - PMC - PubMed

Publication types

Associated data