Cystic fibrosis mutations and genotype–pulmonary phenotype analysis

Abstract

Longitudinal quantitative chest radiography provides a new strategy for CF pulmonary phenotype categorization that should be useful for genotype-phenotype delineation in individual patients and in both epidemiologic studies and clinical trials involving groups of children with CF.

Adopting orphans: comprehensive genetic testing of Mendelian diseases of childhood by next-generation sequencing

“…An empiric goal for target enrichment is to accomplish >30% on-target nucleotides inexpensively, which corresponds to approximately 500-fold enrichment of an approximately 2 million nucleotide target. This was achieved in practice following one round of bait redesign for under-represented exons and decreased bait representation in over-represented exons [18]. An ideal enrichment protocol would give a narrow distribution of target coverage without tails or skewness (indicative of minimal enrichment-associated bias).…”

Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening

“…Genotype was determined as described elsewhere (10) and controlled for using three categories: 1) F508del homozygotes; 2) F508del compound heterozygotes; and 3) those with two other mutations (only 6% of the two cohorts). The molecular techniques used resulted in a very high CF mutation detection rate (99% in Brittany and >95% in Wisconsin) (21, 22).…”

“…Each region also has extensive experience with longitudinal epidemiologic studies (3-9), and the two regions have collaborated on a genotype-pulmonary phenotype project (10). Although early diagnosis through NBS leads to uniformly better nutritional status (11) in all regions that have studied that outcome, there has been very little comparative evaluation of lung disease onset and progression after screening.…”

Newborn Screening for Cystic Fibrosis: A Lesson in Public Health Disparities

“…In other states, the second stage involves a DNA test for CF mutations on the original blood spot. [21] Over 1000 CF mutations have been discovered,[22] and the genetic test may include as few as one mutation (delta F508) or several dozen. [4] Because many mutations are not included, children are referred for sweat tests if only one mutation is found or if the IRT is so high as to be suspicious.…”