The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews |
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| Authors: | M Mei-Zahav P Stafler H Senderowitz L Bentur G Livnat M Shteinberg N Orenstein L Bazak D Prais H Levine M Gur N Khazanov L Simhaev H Eliyahu M Cohen M Wilschanski H Blau H Mussaffi |
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| Institution: | 1. Kathy and Lee Graub Cystic Fibrosis Center and Pulmonary Unit, Schneider Children''s Medical Center of Israel, Petah Tikva, Israel;2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;3. Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel;4. Pediatric Pulmonary Institute, Ruth Rappaport Children''s Hospital, Rambam health Care Campus, Israel;5. Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel;6. Cystic Fibrosis Center, Carmel Hospital, Israel;7. Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel;8. Electrophysiology Laboratory, Hadassah Hebrew University Medical Center, Jerusalem, Israel |
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| Abstract: | BackgroundThe Q359K/T360K mutation, described in Jewish CF patients of Georgian decent, is of questionable clinical significance.MethodsClinical records of patients with the Q359K/T360K mutation from three CF centers were studied for phenotypic expression and putative mechanism of dysfunction. Computer models of mutant CFTR were constructed.ResultsNine patients (4 homozygous) of Georgian Jewish origin were included. Age at diagnosis was 9.4 (0.25–38.2) years, median (range). Sweat chloride was 106?±?13?meq/L, mean?±?SD. Nasal Potential Difference performed in three, was abnormal. All had pulmonary symptoms since early childhood and bronchiectasis. Median FEV1 was 88 (40–121)%. Five had chronic mucoid P. aeruginosa. Homozygous patients were pancreatic insufficient. Enzyme supplementation was initiated at 3.8 (1–14.7) years, median (range). Structural models hint at possible interference of this mutation with transmembrane chloride transport.ConclusionIn our cohort, the Q359K/T360K mutation resulted in a severe CF phenotype, although with residual early CFTR function. The CFTR2 database should consider defining this mutation as CF-causing. |
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| Keywords: | Q359K/T360K mutation Georgian Jews Structural models of CFTR |
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