Chromosomal microarray was ordered on a one-day-old girl with a cardiac anomaly and respiratory insufficiency. Microarray demonstrated a 22 kilobase deletion and a 42 kilobase deletion at chromosome 7q31.2 within the CFTR gene, which is associated with cystic fibrosis (Figure 1).
The correct answer is ...
No, this result cannot differentiate between carrier status and diagnosis of cystic fibrosis.
Cystic fibrosis is an autosomal recessive disease. This means that both copies of the gene must be altered (either through mutations or structural changes such as deletions) to diagnose it. Therefore, it is important to determine if the two deletions within CFTR in this patient are in cis or in trans. If the deletions are in trans, meaning one deletion on each copy of CFTR, this would support a clinical diagnosis of cystic fibrosis or a CF-related disorder. If the deletions are in cis, this may represent carrier status for cystic fibrosis or a clinical diagnosis of cystic fibrosis, or a CF-related disorder if a second hit, such as a mutation, is found on the other allele. However, this microarray data alone does not allow us to determine the configuration of the deletions, making the correct answer this result, "cannot differentiate between carrier status and diagnosis of cystic fibrosis."
Additional follow-up testing is required to determine the configuration of these deletions and differentiate between carrier status and a diagnosis of cystic fibrosis. Chromosomal microarray or multiplex-ligation dependent probe amplification (MLPA) of the CFTR gene in the parents of this patient can provide a clue to how these deletions were inherited. If both deletions are found in a single parent, then they are likely in cis in the patient, but if one was inherited from each parent then the deletions are in trans. If both deletions are found in cis, this is suggestive that the patient is at least a cystic fibrosis carrier. However, further follow-up mutation testing in this patient can help clarify this by determining if there is a second hit within the CFTR gene.
Lauren Choate, Ph.D.
Fellow, Laboratory Genetics and Genomics
Ross Rowsey, Ph.D.
Consultant, Laboratory Genetics and Genomics
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science