Cystic fibrosis mutations with widely variable phenotype: the D1152H example

Pediatr Pulmonol. 2006 Mar;41(3):250-4. doi: 10.1002/ppul.20343.

Abstract

D1152H is a type IV cystic fibrosis transmembrane regulator (CFTR) mutation associated with abnormal chloride gating. Although comprising 5-6% of mutations on genetic screening, clinical reports of cystic fibrosis (CF) are rare, suggesting that the disease is mild, atypical, or even absent. We describe our experience, which contrasts with this assumption, in a retrospective case series encompassing 91 CF patients (74 Jewish) aged 8 months to 56 years, from 2000-2005. Nine patients of varied Jewish ethnic origins were homozygous (2 patients) or compound heterozygous for D1152H with 11 of 182 potential alleles (6%). Five were diagnosed at age 33-49 years. Of 4 infants, 1 was diagnosed by prenatal screening, 1 had a prenatal dilated bowel, and 1 had pulmonary symptoms. Sweat chloride was 28-120 meq/l. Three adults had chronic mucoid Pseudomonas aeruginosa in sputum, and a forced expired volume in 1 sec (FEV1) of 20-55%. One was on bilevel positive airway pressure (BIPAP) ventilation. The infants had pulmonary symptoms that responded well to therapy. All 9 patients had good nutrition, 6 were pancreatic-sufficient, and 3 adults had subclinical pancreatic insufficiency. Three adults had recurrent pancreatitis. None had a bowel obstruction. Two of 3 adult males were fertile. Although asymptomatic at times, the D1152H mutation is associated with a broad clinical spectrum. This information is crucial for genetic counseling. Lung disease may be evident from infancy, and is severe in some adults, although all have outlived the median life expectancy of CF. Hopefully, with early diagnosis and therapy, prognosis can be good. A multicenter study of this mutation is warranted.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / epidemiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Genetic Variation*
  • Heterozygote*
  • Humans
  • Infant
  • Israel / epidemiology
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Sex Factors

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator