BHD mutations, clinical and molecular genetic investigations of Birt–Hogg–Dubé syndrome: a new series of 50 families and a review of published reports
2008

BHD Mutations and Clinical Features in Birt–Hogg–Dubé Syndrome

Sample size: 98 publication 10 minutes Evidence: moderate

Author Information

Author(s): Toro J R, Wei M-H, Glenn G M, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino M J, Pinto P A, Steinberg S M, Schmidt L S, Linehan W M

Primary Institution: National Cancer Institute, National Institutes of Health

Hypothesis

To characterize the BHD mutation spectrum, novel mutations, and new clinical features of one previously reported and 50 new families with BHDS.

Conclusion

BHDS is characterized by a spectrum of mutations and clinical heterogeneity both among and within families.

Supporting Evidence

  • The BHD mutation detection rate was 88% (51/58).
  • Of the 23 different germline mutations identified, 13 were novel.
  • Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p=0.0032).
  • Patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p=0.011).

Takeaway

Birt–Hogg–Dubé syndrome is a genetic condition that can cause skin growths, lung problems, and kidney tumors, and researchers found many new mutations related to this syndrome.

Methodology

Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning.

Limitations

The dataset is too small to examine genotype–phenotype correlations rigorously.

Participant Demographics

The cohort included 89 individuals from 51 families with BHD mutations, consisting of 37 men and 52 women with a median age of 54 years.

Statistical Information

P-Value

0.0032

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1136/jmg.2007.054304

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