Primary spontaneous pneumothorax (PSP) is one of the manifestations of Birt-Hogg-Dube syndrome (BHDS) that is caused by germline mutations of the FLCN gene. There are different types of mutations in FLCN gene and, in addition, patients with PSP should also be screened for mutations in FBN1, COL3A1, CBS, SERPINA1 and TSC1/2 genes which makes the diagnostic procedure complicated and time-consuming. In a new study, Zhang et al. (2016) developed a next generation sequencing (NGS)-based method using Haloplex target enrichment as an easier diagnostic tool. The method successfully detected simultaneously exonic and intronic single-nucleotide variants (SNVs), small indels, large intragenic deletions and determined deletion junctions in all PSP-related genes. The group concluded that the system has a more extensive performance than the commonly used Sanger sequencing and Multiple Ligation-dependent Probe Amplification (MLPA) and a cost analysis showed significant savings using this time-effective and accurate screening system for the molecular diagnosis of BHDS in PSP patients.
This article is freely available to download in the BHD Article Library: Clinical section.
I wonder how long it might take for this to be picked up and used routinely in clinical labs, as a Laboratory Developed Test? Will the current controversy over FDA’s regulation of LDT’s impede this? Current methods (excluding MLPA, which is an extra expense) can’t identify the issue in ~10% of cases that present as BHDS.