Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome

Abstract

BackgroundBirt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder, the main manifestations of which are fibrofolliculomas, renal tumors, pulmonary cysts and recurrent pneumothorax. The known causative gene for BHD syndrome is the folliculin (FLCN) gene on chromosome 17p11.2. Studies of the FLCN mutation for BHD syndrome are less prevalent in Chinese populations than in Caucasian populations. Our study aims to investigate the genotype spectrum in a group of Chinese patients with BHD.MethodsWe enrolled 51 patients with symptoms highly suggestive of BHD from January 2014 to February 2017. The FLCN gene was examined using PCR and Sanger sequencing in every patient, for those whose Sanger sequencing showed negative mutation results, multiplex ligation-dependent probe amplification (MLPA) testing was conducted to detect any losses of large segments.Main resultsAmong the 51 patients, 27 had FLCN germline mutations. In total, 20 mutations were identified: 14 were novel mutations, including 3 splice acceptor site mutations, 2 different deletions, 6 nonsense mutations, 1 missense mutation, 1 small insertion, and 1 deletion of the whole exon 8.ConclusionsWe found a similar genotype spectrum but different mutant loci in Chinese patients with BHD compared with European and American patients, thus providing stronger evidence for the clinical molecular diagnosis of BHD in China. It suggests that mutation analysis of the FLCN gene should be systematically conducted in patients with cystic lung diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0656-7) contains supplementary material, which is available to authorized users.

Pathology of Birt–Hogg–Dubé syndrome: A special reference of pulmonary manifestations in a Japanese population with a comprehensive analysis and review

“…Japanese patients’ mutations are concentrated in exons 11–13 . The mutation c.1285dupC in exon 11, which is the most frequent mutation in Caucasian and Chinese families, is also the most frequent in Japanese families …”

Response to comment on “Birt-Hogg-Dubé syndrome in Korean: clinicoradiologic features and long term follow-up”

“…This also suggest that lung and kidney lesion may be more informative than fibrofolliculomas as diagnostic criteria for BHD syndrome in Asian populations [2]. Although one recent paper mentioned in the correspondence suggested a relatively higher incidence of skin lesions in Japanese patients with BHD syndrome [3], in addition to previous Japanese papers, recent papers including Korean and Chinese patients also suggested low incidence of typical skin lesions in Asian patients with BHD syndrome (20% in Korean and 7.4% in Chinese) [4,5].…”

Characterization of CT scans of patients with Birt-Hogg-Dubé syndrome compared with those of Chinese patients with non-BHD diffuse cyst lung diseases

“…Patients with BHD syndrome were all diagnosed by genetic testing. A total of 20 BHD patients were reported in our previous study (9), and the remaining were diagnosed from 2017 to 2019 (10). Given the relative high incidence of LAM and to avoid the selection bias of the control group, we randomly selected 33 cases using a random number table method from 297 patients with de nite LAM in the DCLD cohort at Peking Union Medical College Hospital during the same period as the selection of BHD patients.…”