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.

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

PATIENTS/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.