Nueva mutación en el síndrome de Birt Hogg Dubé

Sempau, Leticia; Ruiz, Itamar R. G.; González-Morán, Alfonso; Susanna, X.; Hansen, Thomas V.O.

doi:10.1016/j.ad.2010.03.007

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…Only six cases of melanoma have been reported in association with BHDS . The pathogenic mechanism responsible for melanoma seems to be the same as that responsible for the neoplasms in BHDS .…”

Section: Discussionmentioning

confidence: 93%

“…Only six cases of melanoma have been reported in association with BHDS. 1,5,[9][10][11]14 The pathogenic mechanism responsible for melanoma seems to be the same as that responsible for the neoplasms in BHDS. 11 Recent studies have shown that folliculin interacts with the protein FINP1 and its homologue, FINP2, 15 which in turn interact with the protein kinase activated by 5-AMP (AMPK), negatively regulating the mammalian target of rapamycin (mTOR), key for cell proliferation and tumor growth.…”

Section: Discussionmentioning

confidence: 98%

“…The gene responsible for BHDS is located on the short arm of chromosome 17 (17p11.2) and codes for the protein folliculin, which numerous studies suggest acts as an oncogene suppressor protein. [10][11][12] Exon 11 is the most frequently affected, being found in 47% of families with BHDS. 12,13 Most germ cell mutations of FLCN result in a truncated folliculin protein.…”

Section: Discussionmentioning

confidence: 99%

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Birt–Hogg–Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene

et al. 2013

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Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant genodermatosis characterized by the presence of three skin tumors (fibrofolliculomas, trichodiscomas, and acrochordons), together with an increased risk for other tumors, especially renal tumors, caused by a mutation in folliculin, an oncogene suppressor protein. The association of this syndrome with melanoma is very unusual. We report the case of a 54-year-old man with a history of melanoma who had multiple white facial papules. His son also presented similar facial lesions. Histopathologic study showed fibrofolliculomas. These clinical and histopathologic features suggested the diagnosis of BHDS. Genetic study revealed a novel heterozygous mutation p.S185P in exon 6 of the FLCN gene. To date, the association between melanoma and BHDS has rarely been described. As the pathogenic mechanism responsible for melanoma seems to be the same as that responsible for neoplasms in BHDS, the authors consider the melanoma a manifestation of BHDS. Thus, during the periodic follow-up of patients with BHDS, we recommend periodic exhaustive skin examination and excisional biopsy of any suspicious pigmented lesion.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Birt–Hogg–Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene

et al. 2013

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“…45,46 They are predominantly mutations (insertion/deletion, nonsense, splice site) that result in premature protein truncation and presumed loss of FLCN function. In addition, 9 large intragenic deletions or duplications expected to severely disrupt protein structure or, at a minimum, to delete the last exon ( Figure 5 ), 22,29,47,48 and 7 missense mutations resulting in amino acid substitutions have been documented. Nahorski et al evaluated four of these FLCN missense mutations and found that p.Arg239Cys and p.His255Pro FLCN mutants demonstrated reduced protein stability in vitro and the latter mutation supported colony formation in soft agar, whereas p.Val400Ile and p.Lys508Arg mutant proteins demonstrated stability similar to wild-type FLCN and suppressed anchorage independent growth in vitro .…”

Section: Molecular Genetics Of Bhd Syndromementioning

confidence: 99%

Molecular genetics and clinical features of Birt–Hogg–Dubé syndrome

2015

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Birt-Hogg-Dubé (BHD) syndrome is an inherited renal cancer syndrome in which affected individuals are at risk to develop benign, cutaneous fibrofolliculomas, bilateral pulmonary cysts and spontaneous pneumothoraces, and kidney tumors. Bilateral multifocal renal tumors that develop in BHD syndrome are most frequently hybrid oncocytic tumors and chromophobe renal carcinoma, but may present with other histologies. Germline mutations in the FLCN gene on chromosome 17 are responsible for BHD syndrome. BHD-associated renal tumors show inactivation of the wild-type FLCN allele by somatic mutation or chromosomal loss, confirming that FLCN is a tumor suppressor gene that fits the classic two-hit model. FLCN interacts with two novel proteins, FNIP1 and FNIP2, and with AMPK, a negative regulator of mTOR. Studies with FLCN-deficient cell and animal models support a role for FLCN in modulating the AKT-mTOR pathway. Emerging evidence links FLCN with a number of other molecular pathways and cellular processes important for cell homeostasis that are frequently deregulated in cancer, including regulation of TFE3/TFEB transcriptional activity, amino acid-dependent mTOR activation through Rag GTPases, TGF-β signaling, PGC1α-driven mitochondrial biogenesis, and autophagy. Currently, surgical intervention is the only therapy available for BHD-associated renal tumors. Further understanding of the FLCN pathway will hopefully lead to the development of effective forms of therapy for this disease.

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FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax

Ding

Zhu

Zou

et al. 2015

American J of Med Genetics Pt A

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Primary spontaneous pneumothorax (PSP) is a significant clinical problem, affecting tens of thousands patients annually. Germline mutations in the FLCN gene have been implicated in etiology of familial PSP (FPSP). Most of the currently identified FLCN mutations are small indels or point mutations that detected by Sanger sequencing. The aim of this study was to determine large FLCN deletions in PSP families that having no FLCN sequence-mutations. Multiplex ligation-dependent probe amplification (MLPA) assays and breakpoint analyses were used to detect and characterize the deletions. Three heterozygous FLCN intragenic deletions were identified in nine unrelated Chinese families including the exons 1-3 deletion in two families, the exons 9-14 deletion in five families and the exon 14 deletion in two families. All deletion breakpoints are located in Alu repeats. A 5.5 Mb disease haplotype shared in the five families with exons 9-14 deletion may date the appearance of this deletion back to approximately 16 generations ago. Evidences for founder effects of the other two deletions were also observed. This report documents the first identification of founder mutations in FLCN, as well as expands mutation spectrum of the gene. Our findings strengthen the view that MLPA analysis for intragenic deletions/duplications, as an important genetic testing complementary to DNA sequencing, should be used for clinical molecular diagnosis in FPSP.

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Nueva mutación en el síndrome de Birt Hogg Dubé

Cited by 8 publications

References 12 publications

Birt–Hogg–Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene

Birt–Hogg–Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene

Molecular genetics and clinical features of Birt–Hogg–Dubé syndrome

FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax

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