FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax. (21st March 2015)

• Record Type: Journal Article
• Authors: Ding, Yibing; Zhu, Chengchu; Zou, Wei; Ma, Dehua; Min, Haiyan; Chen, Baofu; Ye, Minhua; Pan, Yanqing; Cao, Lei; Wan, Yueming; Zhang, Wenwen; Meng, Lulu; Mei, Yuna; Yang, Chi; Chen, Shilin; Gao, Qian; Yi, Long
• Is Part Of: American journal of medical genetics. Volume 167:Number 5(2015:May)
• Page Start: 1125
• Page End: 1133
• Publication Date: 2015-03-21
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36979
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36979-sec-0001" sec-type="section"> <p>Primary spontaneous pneumothorax (PSP) is a significant clinical problem, affecting tens of thousands patients annually. Germline mutations in the <italic>FLCN</italic> gene have been implicated in etiology of familial PSP (FPSP). Most of the currently identified <italic>FLCN</italic> mutations are small indels or point mutations that detected by Sanger sequencing. The aim of this study was to determine large <italic>FLCN</italic> deletions in PSP families that having no <italic>FLCN</italic> sequence‐mutations. Multiplex ligation‐dependent probe amplification (MLPA) assays and breakpoint analyses were used to detect and characterize the deletions. Three heterozygous <italic>FLCN</italic> 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 <italic>FLCN</italic>, 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. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>