The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews.

BACKGROUND: The Q359K/T360K mutation, described in Jewish CF patients of Georgian decent, is of questionable clinical significance.

METHODS: Clinical 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.

RESULTS: Nine 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.

CONCLUSION: In 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.