title: FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax.
abstract: Primary spontaneous pneumothorax (PSP) is a significant clinical problem, affecting tens of thousands patients annually. Germline mutations in the FLCN gene have been implicated in etiology of familial PSP (FPSP). Most of the currently identified FLCN mutations are small indels or point mutations that detected by Sanger sequencing. The aim of this study was to determine large FLCN deletions in PSP families that having no FLCN sequence-mutations. Multiplex ligation-dependent probe amplification (MLPA) assays and breakpoint analyses were used to detect and characterize the deletions. Three heterozygous FLCN intragenic deletions were identified in nine unrelated Chinese families including the exons 1-3 deletion in two families, the exons 9-14 deletion in five families and the exon 14 deletion in two families. All deletion breakpoints are located in Alu repeats. A 5.5 Mb disease haplotype shared in the five families with exons 9-14 deletion may date the appearance of this deletion back to approximately 16 generations ago. Evidences for founder effects of the other two deletions were also observed. This report documents the first identification of founder mutations in FLCN, as well as expands mutation spectrum of the gene. Our findings strengthen the view that MLPA analysis for intragenic deletions/duplications, as an important genetic testing complementary to DNA sequencing, should be used for clinical molecular diagnosis in FPSP.
authors: Center for Translational Medicine, Nanjing University Medical School, Nanjing, China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China.
authors: Yibing
authors: Y
authors: Ding
authors: Chengchu
authors: C
authors: Zhu
authors: Wei
authors: W
authors: Zou
authors: Dehua
authors: D
authors: Ma
authors: Haiyan
authors: H
authors: Min
authors: Baofu
authors: B
authors: Chen
authors: Minhua
authors: M
authors: Ye
authors: Yanqing
authors: Y
authors: Pan
authors: Lei
authors: L
authors: Cao
authors: Yueming
authors: Y
authors: Wan
authors: Wenwen
authors: W
authors: Zhang
authors: Lulu
authors: L
authors: Meng
authors: Yuna
authors: Y
authors: Mei
authors: Chi
authors: C
authors: Yang
authors: Shilin
authors: S
authors: Chen
authors: Qian
authors: Q
authors: Gao
authors: Long
authors: L
authors: Yi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011030:Pneumothorax / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: BHD syndrome; FLCN gene; deletion/duplication mutation; familiar primary spontaneous pneumothorax