Identification of a novel bhd gene

Abstract

The present disclosure relates to Birt-Hogg-Dubé syndrome, nucleic acids encoding the BHD gene, and methods of using the nucleic acids and proteins encoded thereby. In particular, the present disclosure relates to methods of diagnosing BHD disease and related conditions, such as spontaneous pneumothorax and kidney cancer, and methods of treating BHD skin lesions.

1 . A purified folliculin polypeptide:
 having an amino acid sequence comprising the sequence set forth in SEQ ID NO: 2;   having an amino acid sequence comprising a sequence having at least 95% sequence identity to the sequence set forth in SEQ ID NO: 2;   encoded by a nucleic acid molecule comprising the sequence set forth in SEQ ID NO: 42; or   encoded by a nucleic acid molecule comprising a sequence having at least 90% sequence identity to the sequence set forth in SEQ ID NO: 42.   
     
     
         2 . The polypeptide of  claim 1 , wherein the sequence has at least 98% sequence identity to SEQ ID NO: 2. 
     
     
         3 . The polypeptide of  claim 1 , which comprises SEQ ID NO: 2 with 0 to 10 conservative amino acid substitutions. 
     
     
         4 . The polypeptide of  claim 1 , which is encoded by a nucleic acid sequence having at least 95% sequence identity to SEQ ID NO: 42. 
     
     
         5 . The polypeptide of  claim 1 , which is encoded by a nucleic acid sequence having at least 98% sequence identity to SEQ ID NO: 42. 
     
     
         6 . The polypeptide of  claim 1 , which is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, or SEQ ID NO: 11. 
     
     
         7 . The polypeptide of  claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10 or SEQ ID NO: 12. 
     
     
         8 . A pharmaceutical composition, comprising the purified folliculin polypeptide of  claim 2  and a pharmaceutically acceptable carrier or diluent. 
     
     
         9 . A method of treating BHD disease, comprising administering to a BHD subject an effective amount of the composition of  claim 8 . 
     
     
         10 . An antisense oligonucleotide that inhibits the expression of the folliculin (BHD) polypeptide of  claim 1 .