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Severe cystic fibrosis associated with a deltaF508/R347H + D979A compound heterozygous genotype
1First Department of Internal Medicine, Kagawa Medical University, Japan.
Insights
This study examines twins with cystic fibrosis (CF), a genetic disorder. A rare combination of CFTR gene mutations, R347H and D979A, was identified, contributing to severe CF symptoms.
Area of Science:
- Genetics
- Pediatrics
- Pulmonology
Background:
- Cystic Fibrosis (CF) is a genetic disorder affecting multiple organs.
- Genetic mutations in the CFTR gene are the primary cause of CF.
- Mixed-parentage populations present unique challenges in genetic studies.
Observation:
- A case study of twins with cystic fibrosis (CF) from a Japanese-German mixed-parentage family.
- One twin presented with meconium ileus neonatally; the other developed pulmonary aspergillosis at age 6.
- Both twins received standard CF therapies in the US.
Findings:
- Genetic testing revealed one AF508 mutation and novel missense mutations: R347H in exon 7 and D979A in exon 16 of the CFTR gene.
- The D979A mutation, though rare, was found in combination with R347H.
- This specific mutation combination was associated with severe CF phenotypes in the twins.
Implications:
- Highlights the importance of comprehensive genetic analysis in complex CF cases.
- Suggests that rare CFTR mutations can contribute significantly to disease severity.
- Underscores the need for further research into genotype-phenotype correlations for CFTR mutations.
Abstract:
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.