BHD Research Blog

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94 posts · 26,764 views

BHD Research Blog is the official blog of BHDSyndrome.org, the primary online resource for anyone interested in Birt-Hogg-Dubé Syndrome, a rare genetic condition linked to benign skin growths, collapsed lung and kidney cancers. In the BHD Research Blog, we focus on analysing current research in BHD and related fields, as well as considering wider issues relating to rare diseases.

Lizzie Perdeaux
94 posts

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  • December 16, 2011
  • 04:29 AM
  • 2,628 views

Estimating the risk of pneumothorax and renal cell carcinoma in BHD patients

by Lizzie Perdeaux in BHD Research Blog

Many studies into BHD syndrome have investigated the prevalence of pneumothorax and renal cell carcinoma amongst FLCN mutation carriers. Previous estimations of the RCC risk have varied from 6.5% to 34% (Toro et al., 2008), and for pneumothorax, from 24% … Continue reading →... Read more »

Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J.... (2005) Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. American journal of human genetics, 76(6), 1023-33. PMID: 15852235  

Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, Wei MH, Schmidt LS, Davis L, Zbar B.... (2007) Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome. American journal of respiratory and critical care medicine, 175(10), 1044-53. PMID: 17322109  

Houweling AC, Gijezen LM, Jonker MA, van Doorn MB, Oldenburg RA, van Spaendonck-Zwarts KY, Leter EM, van Os TA, van Grieken NC, Jaspars EH.... (2011) Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. British journal of cancer, 105(12), 1912-9. PMID: 22146830  

Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, & Merino MJ. (2002) Renal tumors in the Birt-Hogg-Dubé syndrome. The American journal of surgical pathology, 26(12), 1542-52. PMID: 12459621  

Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER.... (2009) Birt-Hogg-Dubé syndrome: diagnosis and management. The lancet oncology, 10(12), 1199-206. PMID: 19959076  

  • April 8, 2011
  • 06:29 AM
  • 852 views

The genetics of renal cell carcinoma

by Lizzie Perdeaux in BHD Research Blog

As mentioned in the blog last week, high-throughput DNA sequencing is helping to identify novel mutations related to a number of different genetic disorders. A recent example of this can be seen in a study by Varela et al. (2011), … Continue reading →... Read more »

Kenneth, N., Mudie, S., van Uden, P., & Rocha, S. (2008) SWI/SNF Regulates the Cellular Response to Hypoxia. Journal of Biological Chemistry, 284(7), 4123-4131. DOI: 10.1074/jbc.M808491200  

Reisman, D., Glaros, S., & Thompson, E. (2009) The SWI/SNF complex and cancer. Oncogene, 28(14), 1653-1668. DOI: 10.1038/onc.2009.4  

Varela, I., Tarpey, P., Raine, K., Huang, D., Ong, C., Stephens, P., Davies, H., Jones, D., Lin, M., Teague, J.... (2011) Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature, 469(7331), 539-542. DOI: 10.1038/nature09639  

Xia, W., Nagase, S., Montia, A., Kalachikov, S., Keniry, M., Su, T., Memeo, L., Hibshoosh, H., & Parsons, R. (2008) BAF180 Is a Critical Regulator of p21 Induction and a Tumor Suppressor Mutated in Breast Cancer. Cancer Research, 68(6), 1667-1674. DOI: 10.1158/0008-5472.CAN-07-5276  

  • March 25, 2011
  • 05:44 AM
  • 787 views

Identifying FLCN mutations

by Lizzie Perdeaux in BHD Research Blog

BHD syndrome is caused by small nucleotide alterations in the FLCN gene. A total of 132 different mutations have been identified, which are described in the Folliculin Sequence Variation Database. In a large study of 102 BHD syndrome families, only … Continue reading →... Read more »

Benhammou, J., Vocke, C., Santani, A., Schmidt, L., Baba, M., Seyama, K., Wu, X., Korolevich, S., Nathanson, K., Stolle, C.... (2011) Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome. Genes, Chromosomes and Cancer. DOI: 10.1002/gcc.20872  

  • July 15, 2011
  • 10:56 AM
  • 741 views

Stay connected

by Lizzie Perdeaux in BHD Research Blog

As the BHD community is spread all over the globe, strengthening connections and developing more ways of meeting others is important. At the Third BHD Symposium, people at the Patient and Families session proposed the idea of privately messaging BHDSyndrome.org … Continue reading →... Read more »

  • July 29, 2011
  • 06:13 AM
  • 717 views

Characterisation of pulmonary cysts in BHD syndrome

by Lizzie Perdeaux in BHD Research Blog

A recent paper by Tobino et al. (2011) investigated the differentiation between two cystic lung diseases: BHD syndrome and lymphangioleiomyomatosis (LAM). LAM is a rare lung disease, mainly affecting women, in which multiple cysts develop in the lungs, often leading … Continue reading →... Read more »

  • August 26, 2011
  • 04:00 AM
  • 713 views

Selectively targeting renal cell carcinoma by synthetic lethality

by Lizzie Perdeaux in BHD Research Blog

A major challenge in developing effective cancer therapies is targeting the tumour cells without harming the surrounding healthy tissue. A technique often used to identify such drugs is synthetic lethality. The basis of this technique is that the inhibition of … Continue reading →... Read more »

  • August 12, 2011
  • 04:24 AM
  • 705 views

Lab-profile: Dr Ferenc Müller – University of Birmingham, UK

by Lizzie Perdeaux in BHD Research Blog

As mentioned in last week’s blog post, many more videos have been uploaded on to BHDSyndrome.org, and this week we would like to highlight our interview with Dr Ferenc Müller, a senior lecturer in Genetics at the University of Birmingham … Continue reading →... Read more »

Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, Handley MT, Hadzhiev Y, Masood I, Straatman-Iwanowska AA.... (2011) Loss-of-function mutations in RAB18 cause Warburg micro syndrome. American journal of human genetics, 88(4), 499-507. PMID: 21473985  

Gehrig J, Reischl M, Kalmár E, Ferg M, Hadzhiev Y, Zaucker A, Song C, Schindler S, Liebel U, & Müller F. (2009) Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos. Nature methods, 6(12), 911-6. PMID: 19898487  

Southgate L, Dafou D, Hoyle J, Li N, Kinning E, Critchley P, Németh AH, Talbot K, Bindu PS, Sinha S.... (2010) Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish. Neurogenetics, 11(4), 379-89. PMID: 20390432  

van der Velden YU, Wang L, Zevenhoven J, van Rooijen E, van Lohuizen M, Giles RH, Clevers H, & Haramis AP. (2011) The serine-threonine kinase LKB1 is essential for survival under energetic stress in zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 108(11), 4358-63. PMID: 21368212  

  • September 2, 2011
  • 04:27 AM
  • 681 views

Synthetic lethality as a treatment for HLRCC

by Lizzie Perdeaux in BHD Research Blog

In the blog last week, I introduced synthetic lethality as a potential strategy for cancer therapy which targets tumour cells whilst having no effect on healthy tissue. Another synthetic lethality paper has recently been published in Nature, this time targeting … Continue reading →... Read more »

Frezza C, Zheng L, Folger O, Rajagopalan KN, Mackenzie ED, Jerby L, Micaroni M, Chaneton B, Adam J, Hedley A.... (2011) Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature. PMID: 21849978  

  • April 15, 2011
  • 05:17 AM
  • 680 views

A role for chromatin modifications and DNA repair in renal cell carcinoma

by Lizzie Perdeaux in BHD Research Blog

Following on from the blog last week, which described the identification of PBRM1 mutations in clear-cell RCC (ccRCC), other sequencing studies are also finding new genes that are mutated in ccRCC. For example, Dalgliesh et al. (2010) have identified mutations … Continue reading →... Read more »

Dalgliesh, G., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C.... (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 463(7279), 360-363. DOI: 10.1038/nature08672  

Komori, K., Takagi, Y., Sanada, M., Lim, T., Nakatsu, Y., Tsuzuki, T., Sekiguchi, M., & Hidaka, M. (2009) A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA. Oncogene, 28(8), 1142-1150. DOI: 10.1038/onc.2008.462  

van Haaften, G., Dalgliesh, G., Davies, H., Chen, L., Bignell, G., Greenman, C., Edkins, S., Hardy, C., O'Meara, S., Teague, J.... (2009) Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nature Genetics, 41(5), 521-523. DOI: 10.1038/ng.349  

  • July 22, 2011
  • 05:17 AM
  • 643 views

VHL, HIF and epigenetic modifications in clear cell renal cancer

by Lizzie Perdeaux in BHD Research Blog

In an earlier blog post, Vicki discussed a paper by Dalgliesh et al. (2010), which describes the identification of mutations in a variety of histone modifying genes in clear cell renal cell carcinoma (ccRCC). One of the genes identified codes for a … Continue reading →... Read more »

  • September 16, 2011
  • 10:03 AM
  • 620 views

Tuberous sclerosis complex and autophagy

by Lizzie Perdeaux in BHD Research Blog

Tuberous sclerosis complex (TSC) is a multi-system disorder caused by mutations in the TSC1 or TSC2 genes. As illustrated in the signalling diagram on BHDSyndrome.org, TSC1/2 plays an important role in regulating the mammalian target of rapamycin complex 1 (mTORC1), which is involved … Continue reading →... Read more »

Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C.... (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell, 137(6), 1062-75. PMID: 19524509  

Parkhitko A, Myachina F, Morrison TA, Hindi KM, Auricchio N, Karbowniczek M, Wu JJ, Finkel T, Kwiatkowski DJ, Yu JJ.... (2011) Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proceedings of the National Academy of Sciences of the United States of America, 108(30), 12455-60. PMID: 21746920  

  • August 5, 2011
  • 04:35 AM
  • 609 views

BHDSyndrome.org August Updates

by Lizzie Perdeaux in BHD Research Blog

There have been a few changes to BHDSyndrome.org in the past few weeks. Firstly, the Information Pamphlets are now available for download. Thank you very much to all who participated in the pamphlet survey. Many supportive responses were received from … Continue reading →... Read more »

Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER.... (2009) Birt-Hogg-Dubé syndrome: diagnosis and management. The lancet oncology, 10(12), 1199-206. PMID: 19959076  

  • September 9, 2011
  • 04:00 AM
  • 603 views

Lab-profile: Dr Ravi Nookala – University of Cambridge, UK

by Lizzie Perdeaux in BHD Research Blog

In this month’s lab profile we highlight the work of Dr Ravi Nookala, a structural biologist working in the lab of Professor Sir Tom Blundell in the Department of Biochemistry at the University of Cambridge. Dr Nookala is working on … Continue reading →... Read more »

Nookala RK, Hussain S, & Pellegrini L. (2007) Insights into Fanconi Anaemia from the structure of human FANCE. Nucleic acids research, 35(5), 1638-48. PMID: 17308347  

  • August 19, 2011
  • 04:23 AM
  • 528 views

Familial multiple discoid fibromas

by Lizzie Perdeaux in BHD Research Blog

In 1985, Starink et al. described patients with hereditary multiple trichodiscomas, a skin condition which was proposed to be distinct from Birt-Hogg-Dubé syndrome. However, trichodiscomas are firm, skin-coloured flat or dome-shaped papules, and their similarity to fibrofolliculomas has meant that … Continue reading →... Read more »

Starink TM, Houweling AC, van Doorn MB, Leter EM, Jaspars EH, van Moorselaar RJ, Postmus PE, Johannesma PC, van Waesberghe JH, Ploeger MH.... (2011) Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus. Journal of the American Academy of Dermatology. PMID: 21794948  

Starink TM, Kisch LS, & Meijer CJ. (1985) Familial multiple trichodiscomas. A clinicopathologic study. Archives of dermatology, 121(7), 888-91. PMID: 4015134  

  • July 8, 2011
  • 05:21 AM
  • 360 views

Fumarate hydratase and clear cell renal cancer

by Lizzie Perdeaux in BHD Research Blog

Fumarate hydratase (FH) is a mitochondrial enzyme which is involved in aerobic cellular respiration. As discussed in a previous post, germline mutations of FH can lead to Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC), an autosomal dominant disorder which shares some … Continue reading →... Read more »

  • November 4, 2011
  • 05:12 AM
  • 350 views

Lab-profile: prof. dr. Maurice van Steensel – University Hospital Maastricht

by Lizzie Perdeaux in BHD Research Blog

In this month’s lab-profile we introduce Professor Maurice van Steensel, a Professor of genetic dermatology at the University Hospital Maastricht. Professor van Steensel leads a research group studying the role of FLCN in BHD syndrome and he is also a … Continue reading →... Read more »

Claessens T, Weppler SA, van Geel M, Creytens D, Vreeburg M, Wouters B, & van Steensel MA. (2010) Neuroendocrine carcinoma in a patient with Birt-Hogg-Dubé syndrome. Nature reviews. Urology, 7(10), 583-7. PMID: 20842188  

Menko FH, van Steensel MA, Giraud S, Friis-Hansen L, Richard S, Ungari S, Nordenskjöld M, Hansen TV, Solly J, Maher ER.... (2009) Birt-Hogg-Dubé syndrome: diagnosis and management. The lancet oncology, 10(12), 1199-206. PMID: 19959076  

  • September 23, 2011
  • 04:28 AM
  • 328 views

A case report of localised fibrofolliculomas

by Lizzie Perdeaux in BHD Research Blog

In order to further understand the clinical aspects and symptoms of BHD syndrome, it is important that novel findings discovered during patient analysis are published in case reports. This assists in unravelling genotype-phenotype correlations, and also in identifying trends, for … Continue reading →... Read more »

Alonso-González J, Rodríguez-Pazos L, Fernández-Redondo V, Vega-Gliemmo A, & Toribio J. (2011) Birt-Hogg-Dubé syndrome in a patient with localized fibrofolliculomas and a novel mutation in the FLCN gene. International journal of dermatology, 50(8), 968-71. PMID: 21781069  

Kluger N, Giraud S, Coupier I, Avril MF, Dereure O, Guillot B, Richard S, & Bessis D. (2010) Birt-Hogg-Dubé syndrome: clinical and genetic studies of 10 French families. The British journal of dermatology, 162(3), 527-37. PMID: 19785621  

Schulz T, Ebschner U, & Hartschuh W. (2001) Localized Birt-Hogg-Dubé syndrome with prominent perivascular fibromas. The American Journal of dermatopathology, 23(2), 149-53. PMID: 11285413  

Starink TM, Houweling AC, van Doorn MB, Leter EM, Jaspars EH, van Moorselaar RJ, Postmus PE, Johannesma PC, van Waesberghe JH, Ploeger MH.... (2011) Familial multiple discoid fibromas: A look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus. Journal of the American Academy of Dermatology. PMID: 21794948  

  • March 9, 2012
  • 03:00 AM
  • 323 views

Lab-profile: Professor Arnim Pause – McGill University, Canada

by Lizzie Perdeaux in BHD Research Blog

Our lab-profile for this month introduces the work of Professor Arnim Pause, an Associate Professor in the Department of Biochemistry and a Canada Research Chair in Molecular Oncology at McGill University, Canada. Much of Professor Pause’s early work involved researching … Continue reading →... Read more »

Hudon V, Sabourin S, Dydensborg AB, Kottis V, Ghazi A, Paquet M, Crosby K, Pomerleau V, Uetani N, & Pause A. (2010) Renal tumour suppressor function of the Birt-Hogg-Dubé syndrome gene product folliculin. Journal of medical genetics, 47(3), 182-9. PMID: 19843504  

Iwai K, Yamanaka K, Kamura T, Minato N, Conaway RC, Conaway JW, Klausner RD, & Pause A. (1999) Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proceedings of the National Academy of Sciences of the United States of America, 96(22), 12436-41. PMID: 10535940  

  • October 28, 2011
  • 05:44 AM
  • 317 views

Conference reports

by Lizzie Perdeaux in BHD Research Blog

In July, the Beatson International Cancer Conference took place at The Beatson Institute for Cancer Research in Glasgow, UK. The Beatson Institute is a Cancer Research UK-funded centre which focuses on understanding cancer cell behaviour and developing new therapies and … Continue reading →... Read more »

  • October 7, 2011
  • 04:38 AM
  • 308 views

Video Interview: Dr Derek Lim – University of Birmingham, UK

by Lizzie Perdeaux in BHD Research Blog

As mentioned in our latest newsletter, several new interviews were filmed at the Third BHD Symposium, and have been posted to BHDSyndrome.org. Dr Derek Lim’s work at the University of Birmingham has been described previously, including his contribution to the … Continue reading →... Read more »

Lim, D., Rehal, P., Nahorski, M., Macdonald, F., Claessens, T., Van Geel, M., Gijezen, L., Gille, J., Giraud, S., Richard, S.... (2010) A new locus-specific database (LSDB) for mutations in the folliculin ( ) gene . Human Mutation, 31(1). DOI: 10.1002/humu.21130  

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