In:
Molecular Genetics & Genomic Medicine, Wiley, Vol. 5, No. 3 ( 2017-05), p. 223-236
Abstract:
Preconception carrier screening for cystic fibrosis ( CF ) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan‐population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients. Methods An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next‐generation sequencing of the poly‐T/ TG tracts. Results We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening program. A total of 29/54 (53.7%) mutations were already listed as CF causing by the CFTR 2 database, and only 4/54 (7.4%) were novel. Molecular diagnosis was reached in 78/152 (51.3%) cases. Prenatal diagnosis of 24/78 (30.8%) cases could have been achieved by including all CFTR 2‐causing mutations in the Israeli panel. Conclusions Our data reveal an overwhelming hidden abundance of CFTR gene mutations suggesting that expanded preconception carrier screening might achieve higher preconception detection rates.
Type of Medium:
Online Resource
ISSN:
2324-9269
,
2324-9269
DOI:
10.1002/mgg3.2017.5.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2734884-2
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