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p.R709X heterozygous

Results from gene sequencing and amplification for our child showed one mutation: p.R709X. No other mutations, or variants of unknown significance or gross deletions or duplications were noted.

What phenotypic expression does the heterozygosity for p.R709X bring about? Is my child a carrier.

Thank you in advance fo your help.
Sep 5, 2012
Dear Questioner
Thank you for your question. p.R709X is a mutation which can cause CF and was identified in 1993 by direct sequencing. It is quite a rare mutation, being detected in only one individual from a cohort of 225 CF subjects in an Italian study ( Therefore, your child is a carrier for CF. However, the only way to develop CF symptoms is to have two genes that cause CF.
For your child, it is reassuring that only one mutation has been identified. CF gene sequencing detects approximately 98% of the disease-causing mutations that have been identified in the CFTR gene (Hospital for Sick Children, Toronto. Cystic Fibrosis Mutation Database). However, another mutation may in fact be present, but just not detected using the gene sequencing used.
The risk of carrying a CF mutation depends on ethnic origin. For Caucasians the risk is approximately 1 in 20. On the other hand, the risk for Asian-Americans is of the order of 1 in 90. New mutations are continually being identified.
Often a diagnosis of CF is established without having identified any known culprit mutations (i.e. diagnosis made on the basis of sweat testing in conjunction with typical clinical findings). These rarer CF mutations are initially often not allocated to a specific class of mutation on CF Mutation databases. Furthermore, by virtue of being rare, it can also be challenging to be precise with regard to phenotype, or severity of disease, that the mutation renders in any given individual. In addition, the impact that any given CF mutation has on severity of disease is often determined by the combination of CF mutations, rather than any one mutation in isolation.[1]
It is also important to keep in mind that there is a high variability in phenotype within identical CFTR genotypes.[2] As a definite modifier genes remains to be identified we support consensus statements advising that clinicians should not use genotype alone to predict clinical outcomes at the time of diagnosis.[3]

Dr Cromer
Belfast City Hospital
Reference List

1. Comer, D.M., et al., Clinical phenotype of cystic fibrosis patients with the G551D mutation. QJM, 2009. 102(11): p. 793-8.
2. Loubieres, Y., et al., Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients. Chest, 2002. 121(1): p. 73-80.
3. Castellani, C., et al., Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros, 2008. 7(3): p. 179-96.