%0 Journal Article
%T Apparent Homozygosity of p.Phe508del in CFTR due to a Large Gene Deletion of Exons 4¨C11
%A Vassos Neocleous
%A Panayiotis K. Yiallouros
%A George A. Tanteles
%A Constantina Costi
%A Maria Moutafi
%A Phivos Ioannou
%A Philippos C. Patsalis
%A Carolina Sismani
%A Leonidas A. Phylactou
%J Case Reports in Genetics
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/613863
%X We report a classic cystic fibrosis (CF) boy with a large deletion of exons 4¨C11 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. 1. Introduction Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF conductance transmembrane regulator (CFTR) gene [1, 2]. The CFTR gene spans an approximately 240£¿kb region on chromosome 7q31.3 and codes for 1480 amino acid protein that functions as a cAMP chloride channel in exocrine epithelia [3]. This channel regulates water and ion transport across membranes and is found in the epithelium of secretory epithelial cells in the lungs, liver, pancreas, intestine, reproductive tracts, and sweat glands. Mutations in the CFTR gene are responsible for both the classical and atypical presentations of the disease, including pulmonary disease, pancreatic insufficiency, malabsorption, meconium ileus, failure to thrive, infertility, and elevated concentrations of chloride in sweat [4, 5]. Currently, 1964 CFTR mutations have been listed in the CF database (http://www.genet.sickkids.on.ca/cftr/, accessed 3 February, 2014), 39 of which constitute 90% of mutations found in the Caucasian populations. In patients with CF, the differentiation between true and apparent homozygosity for CFTR mutations is critical for correct prenatal diagnosis of CF, as well as for genetic counseling of the CF patient and his/her family members [6, 7]. Therefore, when
%U http://www.hindawi.com/journals/crig/2014/613863/