Detection of 1733insC mutations in an Asian family with Birt-Hogg-Dubé syndrome.
BACKGROUND
Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients.


OBJECTIVE
This study reports the first Asian family that has been demonstrated to carry a BHD mutation.


METHODS
The proband was a 26-year-old Japanese man with multiple asymptomatic, soft skin-coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle.


RESULTS
Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight-cytosine tract (nucleotides 1733-1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots.


CONCLUSIONS
This study is the first to find the same hot-spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.
Kawasaki
H
H
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan.
Sawamura
D
D
Nakazawa
H
H
Hattori
N
N
Goto
M
M
Sato-Matsumura
K C
KC
Akiyama
M
M
Shimizu
H
H
D000328:Adult; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005350:Fibroma / Q000235:genetics*; D006201:Hair Diseases / Q000235:genetics*; D018859:Hair Follicle; D006801:Humans; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012878:Skin Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins