A 43-year-old man presented with a 15-year history of intermittent pruritic, multiple, skin-colored papules on the face and neck. The lesions developed on the face at first, and then slowly progressed to the neck, covering a 15-year period. Physical examination revealed multiple firm, skin-colored, 2~4 mm sized, papular lesions distributed on the face and neck area (). Except for the cutaneous findings, the patient was otherwise well and had no past history of kidney disease, pneumothorax, or other tumors. The result of the routine laboratory studies and chest x-ray were either normal or negative. His father died after suffering from colon cancer and his younger brother was ill with a pneumothorax. He also stated that his daughters had similar symptoms to his skin lesions.\nA biopsy of one of the facial papules was performed, and the lesion was reminiscent of a fibrofolliculoma by concentric fibrous tissue around follicular epithelium with thin and anastomosing bands separating from adjacent fibrovascular proliferation (). Meanwhile, another section of the same sample showed a relatively well-defined fibrovascular lesion with vascular proliferation and hair follicle at the margin of the lesion, suggesting trichodiscoma (). We studied the molecular genetic status of the FLCN gene after informed consent from the patient. We performed direct amplification of all exons (exon 1-14) of FLCN using previously reported primer sets and PCR conditions. Direct amplification of FLCN from EDTA-treated whole blood was performed using AnyDirectMaxTM Taq REDMix (BioQuest, Seoul, Korea). After gel purification of direct amplicon using a Gel Purification Kit (Solgent, Daejeon, Korea), direct sequencing was performed by ABI 3730XL Sequencer (Applied Biosystems, Foster, CA, USA). Sequencing analysis revealed a heterozygotic c.1285dupC mutation (accession No. NM_144997) in the FLCN gene exon 11 (). This mutation was the same as the previously described 1733insC mutation. This mutation results in producing the truncated protein folliculin, which is caused by a frameshift of the amino acid sequence in the FLCN gene product (). Based on this, we were able to diagnose this patient as BHDS, with support from his clinical and histological findings, family history, and gene mutation revealed by sequencing analysis at genomic DNA level.
A 37-year-old man presented with an asymptomatic right renal mass detected by ultrasonography and CT (Fig. a). No apparent cutaneous lesions were found by careful inspection and palpation of the skin. The patient had a history of spontaneous pneumothorax on both sides and underwent pulmonary bullectomy on the right side at the age of 30. His father had a history of recurrent spontaneous pneumothorax starting at the age of 28 and died of stoke at the age of 63. His uncle had a history of recurrent spontaneous pneumothorax starting at the age of 24 and died of an accident at the age of 56. Open partial nephrectomy was performed on the patient. Histopathologic examination revealed that the tumor was chromophobe RCC, nuclear grade G2, and 2.2 cm × 2.0 cm × 2.0 cm in size (Fig. b).\nGenomic DNA was extracted from blood samples collected from the patient and his family members. Mutation examination revealed that the proband carried a deletion of three bases (CCT) at nucleotides c.770-772 in exon 7 (c.770-772delCCT) (Fig. c), resulting in deletion of the 257th serine residue (p.257delS). No FLCN mutations were found in any other members of the patient’s family.