Severe cystic fibrosis associated with a deltaF508/R347H + D979A compound heterozygous genotype.
This report is concerned with twins with cystic fibrosis (CF). They are of mixed parentage: Japanese mother and German father. One case is presented with meconium ileus as a neonate. The other patient did relatively well until the age of 6 years when she was first hospitalized and diagnosed with pulmonary aspergillosis. They have been receiving standard therapies for CF including digestive enzymes, vitamins and periodic antibiotic therapy in the US. At 19 years of age, they were tested for common mutations and one AF508 cystic fibrosis transmembrane conductance regulator (CFTR) allele was found. Further testing of their CFTR gene as well as those of their Japanese mother and grandmother revealed missense mutations in exon 7 (R347H) and exon 16 (D979A). Although the D979A mutant is very rare, this mutation combination seemed to be responsible for severe CF phenotypes.
Hojo
S
S
First Department of Internal Medicine, Kagawa Medical University, Japan.
Fujita
J
J
Miyawaki
H
H
Obayashi
Y
Y
Takahara
J
J
Bartholomew
D W
DW
D000328:Adult; D000409:Alanine / Q000235:genetics*; D001120:Arginine / Q000235:genetics*; D001216:Asparagine / Q000235:genetics*; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008297:Male; D017354:Point Mutation; D012720:Severity of Illness Index
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006639:Histidine; D001216:Asparagine; D001120:Arginine; D000409:Alanine