Bardet–Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self‐tolerance

Tsyklauri, Oksana; Niederlová, Veronika; Forsythe, Elizabeth; Prasai, Avishek; Drobek, Ales; Kašpárek, Petr; Sparks, Kathryn; Trachtulec, Zdeněk; Procházka, Jan; Sedláček, Radislav; Beales, Philip L.; Huranová, Martina; Štěpánek, Ondřej

doi:10.15252/embr.202050785

Cited by 31 publications

(35 citation statements)

References 105 publications

(120 reference statements)

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“…The potential impact of BBSrelated mutations on the immune system had not been addressed until recently. We have recently reported immune abnormalities in BBS patients, which are associated with a higher incidence of autoimmune diseases (Tsyklauri et al, 2021). Using the Bbs4 −/− mouse model of BBS, we showed that BBS4 deficiency affects mainly the B-cell compartment through a non-intrinsic mechanism that remains to be defined, with only minor effects on the T cell compartment.…”

mentioning

confidence: 88%

The Bardet–Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly

Cassioli

Onnis

Finetti

et al. 2021

Journal of Cell Science

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Components of the intraflagellar transport (IFT) system that regulates the assembly of the primary cilium are co-opted by the non-ciliated T cell to orchestrate polarized endosome recycling and to sustain signaling during immune synapse formation. Here we have investigated the potential role of BBS1, an essential core component of the Bardet-Biedl syndrome complex that cooperates with the IFT system in ciliary protein trafficking, in the assembly of the T cell synapse. We demonstrate that BBS1 allows for centrosome polarization towards the immune synapse. This function is achieved through the clearance of centrosomal F-actin and its positive regulator WASH, a process that we demonstrate to be dependent on the proteasome. We show that BBS1 regulates this process by coupling the 19S proteasome regulatory subunit to the microtubule motor dynein for its transport to the centrosome. Our data identify the ciliopathy-related protein BBS1 as a new player in T cell synapse assembly that acts upstream of the IFT system to set the stage for polarized vesicular trafficking and sustained signaling.

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mentioning

confidence: 88%

The Bardet–Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly

Cassioli

Onnis

Finetti

et al. 2021

Journal of Cell Science

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“…82,83 Tsyklauri et al (2021) reported autoimmune Hashimoto's thyroiditis as having a higher prevalence in BBS patients than in the overall population, probably due to impaired immunity in patients with ciliopathies. 84 At baseline evaluation, the investigation of the thyroid function (the FT4 and TSH levels corroborated with the ultrasonography of the thyroid) is recommended, and then an yearly evaluation of the thyroid gland function. 12 When pregnancy is possible, preconception level of FT4 and TSH should be evaluated in order to modulate levothyroxine hormone replacement during pregnancy and prevent impairment of foetal brain development.…”

Section: Subclinical Hypothyroidismmentioning

confidence: 99%

“…Tsyklauri et al (2021) reported autoimmune Hashimoto’s thyroiditis as having a higher prevalence in BBS patients than in the overall population, probably due to impaired immunity in patients with ciliopathies. 84 …”

Section: Multidisciplinary Approachmentioning

confidence: 99%

Monitoring and Management of Bardet-Biedl Syndrome: What the Multi-Disciplinary Team Can Do

Caba¹,

Florea²,

Braha³

et al. 2022

JMDH

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Bardet -Biedl syndrome is a rare autosomal recessive multisystem non-motile ciliopathy. It has heterogeneous clinical manifestations. It is caused by mutations in 26 genes encoding BBSome proteins, chaperonines, and IFT complex. The main clinical features are: retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary anomalies, and kidney disease. The onset of clinical manifestations is variable which makes the diagnosis difficult in some patients. Because of the multiple system involvement, a multidisciplinary approach is necessary. The purpose of this review is to provide monitoring and management directions for a better approach to these patients.

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“…Subclinical hypothyroidism is a mild form of hypothyroidism characterized by peripheral thyroid hormone levels within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. Hashimoto’s thyroiditis is the most common form of subclinical hypothyroidism and is more prevalent in BBS patients compared to the general population [ 28 , 32 , 33 ].…”

Section: Pleiotropy and Variable Expressivity In Bardet–biedl Syndromementioning

confidence: 99%

Bardet–Biedl Syndrome—Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype–Phenotype Correlations

Florea

Caba

Gorduza

2021

Genes

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Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet–Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.

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Bardet–Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self‐tolerance

Cited by 31 publications

References 105 publications

The Bardet–Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly

The Bardet–Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly

Monitoring and Management of Bardet-Biedl Syndrome: What the Multi-Disciplinary Team Can Do

Bardet–Biedl Syndrome—Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype–Phenotype Correlations

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