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Case Reports in Genetics
Volume 2014, Article ID 613863, 4 pages
http://dx.doi.org/10.1155/2014/613863
Case Report

Apparent Homozygosity of p.Phe508del in CFTR due to a Large Gene Deletion of Exons 4–11

1Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus
2Department of Pediatrics, Hospital “Archbishop Makarios III”, 1474 Nicosia, Cyprus
3Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, 95 Irenes Street, 3041 Limassol, Cyprus
4Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus
5Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus
6Translational Genomics Team, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus

Received 22 November 2013; Accepted 23 December 2013; Published 6 February 2014

Academic Editors: S. Chappell, C.-W. Cheng, and G. Vogt

Copyright © 2014 Vassos Neocleous et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We report a classic cystic fibrosis (CF) boy with a large deletion of exons 4–11 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on one allele and p.Phe508del in exon 10 on the second allele. Both parents of Georgian and Ukrainian background had no personal or family history of the disease. The initial molecular diagnostic investigation identified the patient as homozygous for the p.Phe508del and not compatible with his parent’s genetic status. The possibility of nonpaternity or uniparental disomy (UPD7) was investigated and excluded using microsatellite analysis of highly polymorphic markers on chromosome 7. Array-CGH was also performed on the patient and revealed a male profile with a subtle deletion within the CFTR gene on the long arm (q-arm) of chromosome 7 (7q31.2). The deletion was confirmed by MLPA extending from probe L02380 to probe L14978 (28.7 kb) and that was inherited from his father, while p.PheF508del was inherited from his mother. These data highlight the need for additional testing for large deletions in patients with apparent homozygosity for a mutated CFTR allele that do not match the carrier status of the parents. Not testing can lead to misdiagnosis and misinterpretation of mutation carrier status and the expected penetrance of the disorder.