SEVERE CYSTIC-FIBROSIS ASSOCIATED WITH A DELTA-F508 R347H+D979A COMPOUND HETEROZYGOUS GENOTYPE/

This report is concerned with twins with cystic fibrosis (CF). They ar e of mixed parentage: Japanese mother and German father. One case is p resented with meconium ileus as a neonate. The other patient did relat ively well until the age of 6 years when she was first hospitalized an d diagnosed with pulmonary aspergillosis, They have been receiving sta ndard therapies for CF including digestive enzymes, vitamins and perio dic antibiotic therapy in the US, At 19 years elf age, they were teste d for common mutations and one Delta F508 cystic fibrosis transmembran e conductance regulator (CFTR) allele was found, Further testing of th eir CFTR gene as well as those of their Japanese mother and grandmothe r revealed missense mutations in exon 7 (R347H) and exon 16 (D979A). A lthough the D979A mutant is very rare, this mutation combination seeme d to be responsible for severe CF phenotypes.