genetics question

Question

My daughter was found at age three (she is now nine years old) to have the mutations F508 and 711 3a G. At time she has not experienced any significant lung involvement ( a few episodes of bronchitis) and she is pancreatic sufficient. I would like to ask what is the phenotype and the relative progress of these children with these mutations? Is this atypical CF? Is there any information on this second mutation?
Thank you

Answer

Thank you for your question.
The 711+3a->g mutation has a world wide prevalence of 1.15% and is present in British, Greek, Italian and Macedonian populations. (www.findbase.org). In order to determine if your daughter has classic CF or non classic CF (atypical CF), we would need to know the results of a sweat test. If the sweat test result is positive, this indicates classic CF. If the result is borderline, this indicates non classic CF. (De Boeck et al, 2006). The 711+3a->g mutation is usually associated with milder disease, (Castellani et al, 2008), yet with variable disease expression, from minimal lung disease, pancreatic sufficiency and male fertility to a relatively severe disease in all involved organs. Therefore, the course of the disease in this individual case cannot only be predicted according to the knowledge of the underlying mutation; therefore regular clinical surveillance in a CF center is inevitable in order to diagnose the extent of the involvment of other other organs and to initiate treatment early.

References
Castellani et al, 2008. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. Journal of Cystic Fibrosis;7:179-196).
De Boeck K, Wilschanski M, Castellani C, Taylor C, CuppensH, Dodge J, Sinaasappel M (2006). Cystic Fibrosis: terminology and diagnostic algorithms. Thorax;61:627-635.

Best wishes
Lauren Wilson
Stuart Elborn

03.08.2010

The answer is edited by: Prof Stuart Elborn

14.09.10 To give some more information on the mutation 711+3a->g, which belongs to the splicing mutations, here is the citation from the above mentioned Castellani paper: "Splicing mutations that still result in a fraction of correctly spliced transcripts, together with aberrantly spliced transcripts, may belong to the CF-causing or CFTR-related disorders associated group. Patients carrying these mutations often have a relatively mild phenotype, yet with variable disease expression, from minimal lung disease, pancreatic sufficiency and male fertility to a relatively severe disease in all involved organs. "
D. d'Alquen