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Cystic fibrosis mutations with widely variable phenotype: the D1152H example
H Mussaffi1, D Prais, M Mei-Zahav
1Kathy and Lee Graub Cystic Fibrosis Center and Pulmonary Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Pediatric Pulmonology
|January 24, 2006
Summary
The D1152H mutation in cystic fibrosis transmembrane regulator (CFTR) can cause significant lung disease and other symptoms, even in adults diagnosed later in life. Early diagnosis and treatment are crucial for improving outcomes in patients with this CFTR mutation.
Area of Science:
- Genetics
- Pulmonology
- Medical Research
Background:
- The D1152H mutation in the cystic fibrosis transmembrane regulator (CFTR) gene is identified in 5-6% of genetic screenings for cystic fibrosis (CF).
- Clinical manifestations of CFTR D1152H are often considered mild or atypical, with rare reports.
- This contrasts with observations in a cohort of patients with the D1152H mutation.
Purpose of the Study:
- To describe the clinical spectrum of cystic fibrosis transmembrane regulator (CFTR) D1152H mutation.
- To highlight the variability in disease presentation and severity.
- To emphasize the importance of this mutation in genetic counseling and patient management.
Main Methods:
- Retrospective case series of 91 cystic fibrosis (CF) patients diagnosed between 2000-2005.
- Analysis of 9 patients (varied Jewish ethnic origins) who were homozygous or compound heterozygous for D1152H.
- Review of clinical data including age at diagnosis, symptoms, sweat chloride levels, pulmonary function, pancreatic function, and other complications.
Main Results:
- Nine patients (homozygous or compound heterozygous for D1152H) were identified, representing 6% of potential alleles.
- Diagnosis ages varied widely, from infancy (including prenatal detection) to adulthood (33-49 years).
- Clinical presentations included pulmonary symptoms from infancy, severe adult lung disease (FEV1 20-55%, Pseudomonas aeruginosa), pancreatitis, and good nutritional status. Sweat chloride levels ranged from 28-120 meq/l.
Conclusions:
- The D1152H CFTR mutation is associated with a broad clinical spectrum, contrary to previous assumptions.
- Lung disease can be severe and present from infancy, with significant impact in adulthood.
- Early diagnosis and therapy are recommended to improve prognosis, underscoring the need for multicenter studies.