A retrospective two centre study of Birt-Hogg-Dube syndrome reveals a pathogenic founder mutation in FLCN in the Swedish population

Birt-Hogg-Dube syndrome (BHDS) (MIM: 135150) is a rare autosomal dominant disorder with variable penetrance, caused by pathogenic variants in the FLCN gene. Only a few hundreds of families have so far been described in the literature. Patients with BHDS present with three distinct symptoms: fibrofolliculomas, pneumothorax due to lung cyst formation, and increased lifetime risk of kidney tumours. The aim of the current study was to estimate the incidence of BHDS in the Swedish population and further describe the clinical manifestations and their frequency. Splice variant c.779+1G>T was the most common pathogenic variant, found in 57% of the families, suggesting this may be a founder mutation in the Swedish population. This was further investigated using haplotype analysis in 50 families that shared a common haplotype. Moreover, according to gnomAD the carrier frequency of the c.779+1G>T variant has been estimated to be 1/3265 in the Swedish population, however our data suggest that the carrier frequency in the Swedish population may be significantly higher. These findings should raise awareness among physicians of different specialties to patients presenting with fibrofolliculomas, pneumothorax and/or kidney tumours. We also stress the importance of consensus recommendations regarding diagnosis and clinical management of this, not that uncommon, syndrome.

Baranowska Korberg, IzabellaUppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden.(Swepub:uu)izaba878 (author)
Tsiaprazis, StefanosUppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden.(Swepub:uu)stets501 (author)
Bjorck, ErikKarolinska Institutet (author)
Tham, EmmaKarolinska Institutet (author)
Poluha, AnnaUppsala universitet,Medicinsk genetik och genomik,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden.(Swepub:uu)annpo486 (author)
Hellstrom Pigg, MarittaUppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden. (author)
Paulsson-Karlsson, YlvaUppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden. (author)
Nordenskjold, MagnusKarolinska Institutet (author)
Johansson-Soller, MariaKarolinska Institutet (author)
Aravidis, ChristosUppsala universitet,Medicinsk genetik och genomik,Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden.(Swepub:uu)chrar109 (author)
Karolinska InstitutetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

By the author/editor: Lagerstedt-Robin ...; Baranowska Korbe ...; Tsiaprazis, Stef ...; Bjorck, Erik; Tham, Emma; Poluha, Anna; show more...; Hellstrom Pigg, ...; Paulsson-Karlsso ...; Nordenskjold, Ma ...; Johansson-Soller ...; Aravidis, Christ ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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