Characterization of a recurrent 3.8kb deletion involving exons 17a and 17b within the CFTR gene

J Cyst Fibros. 2013 May;12(3):290-4. doi: 10.1016/j.jcf.2012.08.017. Epub 2012 Sep 19.

Abstract

Background: Large deletions within CFTR have been estimated to constitute 1-2% pathogenic alleles, but the occurrence could be much higher in classical cystic fibrosis (CF) patients with one mutation detectable by the routine screening/sequencing work-up. Currently, evaluation of major CFTR rearrangements is not included in the mutation analysis for the reproductive partner of a CF patient/carrier.

Methods: Exon sequencing and Multiplex Ligation-dependent Amplification (MLPA) analyses were used to make a molecular diagnosis of two unrelated CF patients. Long PCR, restriction mapping, cloning, and hot start sequencing were employed to accurately annotate the rearrangement junctions.

Results: Both patients had a heterozygous single amino acid deletion mutation identified by sequencing, and a heterozygous deletion of CFTR exons 17a and 17b detected by MLPA. Molecular characterization of the rearrangement breakpoints indicated that the two patients had an identical complex c.2988+1616_c.3367+356del3796ins62 change, flanked by a pair of perfectly inverted repeats of 32 nucleotides.

Conclusions: The c.2988+1616_c.3367+356del3796ins62 complex rearrangement is a recurrent mutation from patients of different ethnic backgrounds. This mutation can be detected through a simple PCR based analysis.

Publication types

  • Case Reports

MeSH terms

  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Exons / genetics
  • Female
  • Humans
  • Infant
  • Male
  • Sequence Deletion*
  • Young Adult

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator