Birt-Hogg-Dubé syndrome in two Chinese families with mutations in the FLCN gene

Abstract

BackgroundBirt-Hogg-Dubé syndrome is an autosomal dominant hereditary condition caused by mutations in the folliculin-encoding gene FLCN (NM_144997). It is associated with skin lesions such as fibrofolliculoma, acrochordon and trichodiscoma; pulmonary lesions including spontaneous pneumothorax and pulmonary cysts and renal cancer.MethodsGenomic DNA was extracted from peripheral venous blood samples of the propositi and their family members. Genetic analysis was performed by whole exome sequencing and Sanger sequencing aiming at corresponding exons in FLCN gene to explore the genetic mutations of these two families.ResultsIn this study, we performed genetic analysis by whole exome sequencing and Sanger sequencing aiming at corresponding exons in FLCN gene to explore the genetic mutations in two Chinese families. Patients from family 1 mostly suffered from pneumothorax and pulmonary cysts, several of whom also mentioned skin lesions or kidney lesions. While in family 2, only thoracic lesions were found in the patients, without any other clinical manifestations. Two FLCN mutations have been identified: One is an insertion mutation (c.1579_1580insA/p.R527Xfs on exon 14) previously reported in three Asian families (one mainland family and two Taiwanese families); while the other is a firstly reviewed mutation in Asian population (c.649C > T / p.Gln217X on exon 7) that ever been detected in a French family.ConclusionsOverall, The detection of these two mutations expands the spectrum of FLCN mutations and will provide insight into genetic diagnosis and counseling of Birt-Hogg-Dubé syndrome.

Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families

“…1). Using the study criteria outlined above, 221 cases from 120 families with BHDS were included in the final analysis, which were reported in 20 papers (Table 1) [8][9][10][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. In 2008, the first 10 families with spontaneous pneumothorax and positive FLCN mutations in the Chinese population were described by a research team at Nanjing University [8].…”

Importance of Family History in the Era of Exome Analysis: A Report of a Family with Multiple Concurrent Genetic Diseases

“…The second condition found to be segregating within the family is BHDS. BHDS is caused by pathogenic variants in FLCN and is inherited in an autosomal dominant manner [5, 11]. FLCN encodes folliculin, a tumor suppressor protein expressed in a variety of tissues, including the skin, distal nephron of the kidney, and type 1 pneumocytes of the lung [11].…”

“…OPMD is tested for by looking for pathogenic variants in PAPBPN1, defined as an expansion of a (GCN)10 repeat in the first exon to (GCN)12–17 repeats [4]. BHDS is tested for by looking for mutations in the FLCN gene, several of which have been described [5].…”

EGF Stimulates Rab35 Activation and Gastric Cancer Cell Migration by Regulating DENND1A-Grb2 Complex Formation

“…In addition, no studies have revealed its role in tumors. However, the same family protein FLCN has been studied in breast cancer, kidney cancer and cervical cancer ( Zheng et al, 2017 ; Hou et al, 2018 ; Sattler et al, 2018 ). In view of this, our studies in gastric cancer have shown that DENND1A exerts GEF action during the activation of Rab35 stimulated by EGF, and through its interaction with Grb2, it can regionally recruit activated Rab35 and then promote the migration of tumor cells.…”