BHD Literature Database Updated

The literature Database has been updated with the following papers:

Basic Research:

Zhang et al. show that FLCN-null renal cell carcinoma cell lines show decreased survival following irradiation, due to an increase in autophagic cell death caused by dysregulated MEK-ERK signalling. Treatment of cells with autophagy inhibitors abrogated the effects of irradiation, whilst Rapamycin increased cells’ sensitivity to irradiation.

Martina et al. show that under amino acid sufficiency, active GTP-bound Rag proteins recruit TFE3 to the lysosome, where it is phosphorylated at S311 by mTORC1. During amino acid depletion, the Rag proteins become inactive, mTORC1 is released from the lysosome, TFE3 is not phosphorylated and can translocate to the nucleus where it activates the transcription of lysosome and autophagy genes. Knock down of FLCN led to hypo-phosphorylation of TFE3 by mTORC1. Thus, FLCN inhibits autophagy by facilitating the phosphorylation of TFE3.

Clinical Research:

Kumasaka et al. analysed 229 lung cysts in resections from 50 BHD patients and compared them with 117 lung cysts from 34 PSP patients, comparing samples for number, size, location and presence of inflammation. They found that BHD lung cysts were found in both subpleural and intrapulmonary areas; often found at interlobular septa and 40% had venules; and only showed signs of inflammation if located in the subpleura. The authors suggest that loss of FLCN causes alveoli walls to become weak and vulnerable to disruption by mechanical stress during breathing, which causes cysts to form. Furthermore, based on the observation that inflamed cysts tended to be larger and located in the sub-pleura, they suggest that pneumothorax inflames existing cysts, causing them to grow and subsume neighbouring cysts. This paper is available to download from the BHD Articles Library: Clinical Research.

Review:

Koul reviews the literature regarding the epidemiology and clinical characteristics of pneumothorax in BHD.

Bar-Peled and Sabatini review the regulation of mTORC1 by amino acids, including the role of FLCN in activating mTORC1 in response to amino acid restimulation.

Case study:

Kolb et al., report the case of a 32 year old woman who presented with a progressive exertional dyspnea and an abnormal chest CT scan. Her medical history included two prior pneumothoraces at the age of 19 and a family history of spontaneous pneumothorax and renal cancer. Physical examination revealed the presence of facial papules, lung cysts, but no renal abnormalities. Genetic testing confirmed a diagnosis of BHD.

Onuki et al. present the case of a Japanese family with BHD syndrome who present with recurrent pneumothorax, but did not show detectable lesions in the lung with radio-imaging. Video-assisted thoracic surgery revealed the presence of multiple diffuse microcysts on the pleura, suggesting that radiologically indeterminate cysts may be able to cause pneumothorax.

Escuissato et al. report the case of a 66 year old Brazilian man who had a family history of kidney cancer. Physical and diagnostic examination confirmed the presence of skin coloured papules on the face and neck, multiple lung cysts in the lung bases and a renal tumour. The patient and his family were diagnosed with BHD and referred for genetic counselling and oncological follow up. It is not stated whether the patient received a genetic diagnosis of BHD. This paper is available to download from the BHD Articles Library: Clinical Research.

Letters:

Fabré et al. reply to the letter from Johannesma et al. concerning the original Fabre et al. study investigating the histological differences between smoking-associated lung pathology and BHD-associated lung cysts.

To find out more, the latest version of the database is available to download here.

 

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