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Birt-hogg-dubé syndrome is a novel ciliopathy

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Birt-hogg-dubé syndrome is a novel ciliopathy. / Luijten, Monique N.H.; Basten, Sander G.; Claessens, Tijs et al.
In: Human Molecular Genetics, Vol. 22, No. 21, 01.11.2013, p. 4383-4397.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Luijten, MNH, Basten, SG, Claessens, T, Vernooij, M, Scott, CL, Janssen, R, Easton, JA, Kamps, MAF, Vreeburg, M, Broers, JLV, Geel, MV, Menko, FH, Harbottle, RP, Nookala, RK, Tee, AR, Land, SC, Giles, RH, Coull, BJ & van Steensel, MAM 2013, 'Birt-hogg-dubé syndrome is a novel ciliopathy', Human Molecular Genetics, vol. 22, no. 21, pp. 4383-4397. https://doi.org/10.1093/hmg/ddt288

APA

Luijten, M. N. H., Basten, S. G., Claessens, T., Vernooij, M., Scott, C. L., Janssen, R., Easton, J. A., Kamps, M. A. F., Vreeburg, M., Broers, J. L. V., Geel, M. V., Menko, F. H., Harbottle, R. P., Nookala, R. K., Tee, A. R., Land, S. C., Giles, R. H., Coull, B. J., & van Steensel, M. A. M. (2013). Birt-hogg-dubé syndrome is a novel ciliopathy. Human Molecular Genetics, 22(21), 4383-4397. https://doi.org/10.1093/hmg/ddt288

Vancouver

Luijten MNH, Basten SG, Claessens T, Vernooij M, Scott CL, Janssen R et al. Birt-hogg-dubé syndrome is a novel ciliopathy. Human Molecular Genetics. 2013 Nov 1;22(21):4383-4397. doi: 10.1093/hmg/ddt288

Author

Luijten, Monique N.H. ; Basten, Sander G. ; Claessens, Tijs et al. / Birt-hogg-dubé syndrome is a novel ciliopathy. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 21. pp. 4383-4397.

Bibtex

@article{f99bf23f831b48f58c92e1dea1f11dcd,
title = "Birt-hogg-dub{\'e} syndrome is a novel ciliopathy",
abstract = "Birt-Hogg-Dub{\'e} (BHD) syndromeis an autosomal dominant disorder where patients are predisposed to kidney cancer, lung and kidney cysts and benign skin tumors. BHD is caused by heterozygous mutations affecting folliculin (FLCN), a conserved protein that is considered a tumor suppressor. Previous research has uncovered multiple roles for FLCN in cellular physiology, yet it remains unclear how these translate to BHD lesions. Since BHD manifests hallmark characteristics of ciliopathies, we speculated that FLCN might also have a ciliary role. Our data indicate that FLCN localizes to motile and non-motile cilia, centrosomes and the mitotic spindle. Alteration of FLCN levels can cause changes to the onset of ciliogenesis, without abrogating it. In threedimensional culture, abnormal expression of FLCN disrupts polarized growth of kidney cells and deregulates canonical Wnt signalling. Our findings further suggest that BHD-causing FLCN mutants may retain partial functionality. Thus, several BHD symptoms may be due to abnormal levels of FLCN rather than its complete loss and accordingly, we show expression of mutant FLCN in a BHD-associated renal carcinoma. We propose that BHD is a novel ciliopathy, its symptoms at least partly due to abnormal ciliogenesis and canonical Wnt signalling.",
author = "Luijten, {Monique N.H.} and Basten, {Sander G.} and Tijs Claessens and Marigje Vernooij and Scott, {Claire L.} and Renske Janssen and Easton, {Jennifer A.} and Kamps, {Miriam A.F.} and Maaike Vreeburg and Broers, {Jos L.V.} and Geel, {Michel van} and Menko, {Fred H.} and Harbottle, {Richard P.} and Nookala, {Ravi K.} and Tee, {Andrew R.} and Land, {Stephen C.} and Giles, {Rachel H.} and Coull, {Barry J.} and {van Steensel}, {Maurice A.M.}",
year = "2013",
month = nov,
day = "1",
doi = "10.1093/hmg/ddt288",
language = "English",
volume = "22",
pages = "4383--4397",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "21",

}

RIS

TY - JOUR

T1 - Birt-hogg-dubé syndrome is a novel ciliopathy

AU - Luijten, Monique N.H.

AU - Basten, Sander G.

AU - Claessens, Tijs

AU - Vernooij, Marigje

AU - Scott, Claire L.

AU - Janssen, Renske

AU - Easton, Jennifer A.

AU - Kamps, Miriam A.F.

AU - Vreeburg, Maaike

AU - Broers, Jos L.V.

AU - Geel, Michel van

AU - Menko, Fred H.

AU - Harbottle, Richard P.

AU - Nookala, Ravi K.

AU - Tee, Andrew R.

AU - Land, Stephen C.

AU - Giles, Rachel H.

AU - Coull, Barry J.

AU - van Steensel, Maurice A.M.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Birt-Hogg-Dubé (BHD) syndromeis an autosomal dominant disorder where patients are predisposed to kidney cancer, lung and kidney cysts and benign skin tumors. BHD is caused by heterozygous mutations affecting folliculin (FLCN), a conserved protein that is considered a tumor suppressor. Previous research has uncovered multiple roles for FLCN in cellular physiology, yet it remains unclear how these translate to BHD lesions. Since BHD manifests hallmark characteristics of ciliopathies, we speculated that FLCN might also have a ciliary role. Our data indicate that FLCN localizes to motile and non-motile cilia, centrosomes and the mitotic spindle. Alteration of FLCN levels can cause changes to the onset of ciliogenesis, without abrogating it. In threedimensional culture, abnormal expression of FLCN disrupts polarized growth of kidney cells and deregulates canonical Wnt signalling. Our findings further suggest that BHD-causing FLCN mutants may retain partial functionality. Thus, several BHD symptoms may be due to abnormal levels of FLCN rather than its complete loss and accordingly, we show expression of mutant FLCN in a BHD-associated renal carcinoma. We propose that BHD is a novel ciliopathy, its symptoms at least partly due to abnormal ciliogenesis and canonical Wnt signalling.

AB - Birt-Hogg-Dubé (BHD) syndromeis an autosomal dominant disorder where patients are predisposed to kidney cancer, lung and kidney cysts and benign skin tumors. BHD is caused by heterozygous mutations affecting folliculin (FLCN), a conserved protein that is considered a tumor suppressor. Previous research has uncovered multiple roles for FLCN in cellular physiology, yet it remains unclear how these translate to BHD lesions. Since BHD manifests hallmark characteristics of ciliopathies, we speculated that FLCN might also have a ciliary role. Our data indicate that FLCN localizes to motile and non-motile cilia, centrosomes and the mitotic spindle. Alteration of FLCN levels can cause changes to the onset of ciliogenesis, without abrogating it. In threedimensional culture, abnormal expression of FLCN disrupts polarized growth of kidney cells and deregulates canonical Wnt signalling. Our findings further suggest that BHD-causing FLCN mutants may retain partial functionality. Thus, several BHD symptoms may be due to abnormal levels of FLCN rather than its complete loss and accordingly, we show expression of mutant FLCN in a BHD-associated renal carcinoma. We propose that BHD is a novel ciliopathy, its symptoms at least partly due to abnormal ciliogenesis and canonical Wnt signalling.

U2 - 10.1093/hmg/ddt288

DO - 10.1093/hmg/ddt288

M3 - Journal article

C2 - 23784378

AN - SCOPUS:84885692467

VL - 22

SP - 4383

EP - 4397

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 21

ER -