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  • Nonsense mutations in folliculin presenting as isolated familial spontaneous pneumothorax in adults
    Graham, Randall B. ...
    Rationale: Approximately 10% of patients who have a spontaneous pneumothorax have a positive family history. Objectives: We sought to identify DNA sequencevariations that confer susceptibility to ... pneumothoraces. Methods: We collected 12 families that had at least 2 first-degree relatives with a spontaneous pneumothorax. All affected family members had no obvious stigmata of known genetic disorders associated with pneumothoraces. We used haplotype analysis, DNA sequencing, and restriction fragment analysis of mutations to evaluate the individuals in these families. Main Results: In 2 of the 12 families the disorder cosegregated with markers flanking a candidate locus, FLCN. Sequencing the linked alleles revealed 2 mutations predicted to introduce premature stop codons in 2 of the 12 families. Most mutations in FLCN cause a rare disease, Birt-Hogg-Dube syndrome, characterized by autosomaldominant inheritance of multiple benign skin lesions, renal tumors, pulmonary blebs, and pneumothoraces. None of the family members with the nonsense mutations had the skin manifestations of Birt-Hogg-Dube syndrome or renal cancer. Pathologic examination of lung tissue from three affected nonsmokers revealed blebs and underlying emphysema. Conclusions: Isolated familial spontaneous pneumothorax can be caused by mutations of the FLCNgene. Because development of a pneumothorax and/or pulmonary blebs may be the earliest or the only clinical manifestation of FLCN mutations, pulmonologists should be alert to the contribution of this gene toward this familial form of emphysema.
    Vrsta gradiva - članek, sestavni del
    Leto - 2005
    Jezik - angleški
    COBISS.SI-ID - 20199129