A novel familial germline mutation in the initiator codon of the BHD gene in a patient with Birt-Hogg-Dubé syndrome

Abstract

Birt-Hogg-Dubé syndrome (BHD) (OMIM 135150) is an inherited autosomal dominant genodermatosis that predisposes individuals to the development of fibrofolliculomas, trichodiscomas and acrochordons of the face, neck and upper trunk. 1 There is also an increased risk for lung cysts, spontaneous pneumothorax and renal carcinomas in affected people, and some patients may also develop colorectal polyps and cancers. 2-4 The disease is caused by germline mutations in the BHD (also known as FLCN) gene located in 17p11.2 encoding folliculin, a new protein with unknown function. 5 We report a patient with apparently sporadic BHD in which molecular analysis subsequently revealed a novel germline mutation in the initiator codon of the BHD gene in the proband and her son. Case and methods

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

“…5 7 – 15 Of a total of 40 BHD germline mutations reported to date, only four mutations (c.1065-6delGCinsTA, c. 1733insC, c. 1733delC and 1884C>T) were reported by both the NCI BHDS group and other investigators 4 – 9 12 – 14. A family with the c.875delC mutation was described in two different studies 7 8 .…”

“…A family with the c.875delC mutation was described in two different studies 7 8 . BHD mutations have been reported affecting all translated exons,4 – 14 with the exception of exons 8 and 10 4 – 15. Exon 11 was the most frequent site of mutations (c.1733insC/1733delC, c.1755G>C) present in 125 individuals from 40 unrelated BHDS families 4 – 9 12 – 14.…”

“…BHD mutations have been reported affecting all translated exons,4 – 14 with the exception of exons 8 and 10 4 – 15. Exon 11 was the most frequent site of mutations (c.1733insC/1733delC, c.1755G>C) present in 125 individuals from 40 unrelated BHDS families 4 – 9 12 – 14. The hot spot mutation (c.1733insC or c.1733delC) was the most common BHD mutation reported to date in a total of 124 individuals from 39 BHDS families 4 – 9 12 – 14.…”

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene

“…The database lists previously published point mutations, deletions, duplications and splice site mutations in the FLCN gene (Bessis et al, 2006;Cho et al, 2008;Frohlich et al, 2008;Gad et al, 2007,Graham et al, 2005Gunji et al, 2007;Imada et al, 2009;Kawasaki et al, 2005;Khoo et al, 2002;Kim et al, 2008;Lamberti et al, 2005;Leter et al, 2008;Murakami et al, 2007;Nickerson et al, 2002;Painter et al, 2005;Palmirotta et al, 2008;Ren et al, 2008;Schmidt et al, 2005;Toro et al, 2008;van Steensel et al, 2007;Woodward et al, 2008). In addition 10 previously unpublished novel mutations/variants are included.…”

“…These cysts can be detected usually from the age of 20 years and in about 24% of patients, these cysts are associated with spontaneous pneumothorax Toro et al, 1999;Toro et al, 2007;Zbar et al, 2002). However, one child with a germline FLCN (MIM# 607273) mutation presented with a spontaneous pneumothorax at the age of 7 years (Bessis et al, 2006). The most serious complication of BHD is renal cancer.…”