Contributed by Arivarasan Karunamurthy, MD. and Jeffrey A. Kant, MD, PhD
A 20 year old male with persistent cough was evaluated for surgical and anesthesia risk. The patient did not report fever, weight loss or night sweats. He was a smoker but quit 5yrs ago. No history of exposures to asbestos or industrial dusts was elicited.
The patient was never hospitalized for pneumonia as a child but was diagnosed with bronchiectasis at the age of 15 and underwent bronchoscopy every 3-4 month since then. He also reported a history of blunt chest injury from trauma at age 19, with chest x-ray showing patchy areas of airspace opacity involving predominantly the upper lobes bilaterally, these findings interpreted as suggestive of upper lobe bronchiectasis. Family history was negative for cystic fibrosis or bronchiectasis. His previous sputum cultures for mycobacterium tuberculosis were negative as was testing for alpha1 antitrypsin deficiency.
Physical examination showed a clear chest with no rales, rhonchi, or wheezes. No organomegaly or adenopathy were identified. A CT chest study showed upper lobe predominant bronchiectatic changes. Pulmonary function tests displayed a mildly reduced FEV1/FVC ratio. Laboratory investigations did not reveal any significant abnormalities except for elevated serum IgG and IgE. ACE was within normal limits.
Based on these findings the physician considered bronchiectasis of unknown etiology; peripheral blood was sent for genetic testing for cystic fibrosis (CF).
MOLECULAR GENETIC STUDIES
A population-based CF carrier screening assay that detects thirty-two mutations, including the twenty-three core mutations recommended by the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) was performed.
Using an oligonucleotide ligation assay (OLA) following multiplex-polymerase chain reaction (PCR) amplification of specific CF gene regions and separation of fluorescent allele-specific reaction products by capillary electrophoresis, the patient tested as a compound heterozygote for the common CFTR Delta F508 mutation as well as the R117H mutation. Intron 8 poly T results were reported because of the positive R117H result; the patient was heterozygous for the 5T and 9T alleles. Because of the common association of the intron 8 9T sequence on chromosomes carrying a DeltaF508 mutation, the patient was presumed to carry the 5T allele in cis with the R117H mutation.