c.3773_3774insT (p.Leu1258PhefsX7)

Question

Our son has the above mentioned mutation as well as Delta F508. The latter is known to me but for the one that is mentioned in the subject line I could not find any information. Considering these mutations, what can we expect (concerning the course of the disease and the medication)?

Answer

Hello,

The mutation c.3773_3774insT (p.Leu1258PhefsX7) is relatively frequent in CF and was originally known as 3905insT. It is a so called frame-shift mutation. This is an insertion of a single nucleotide which leads as of position 1258 (amino acid leucine in CFTR proteine) to a switch of 7 amino acids and following to the stop of the protein synthesis. As a consequence of such mutations, CFTR proteine can frequently not be detected on a cellular level (so called class 1 mutation). Unlike as with so called stop-mutations (which are also mostly class 1 mutations), Ataluren, a new drug for treating CF patients with stop-mutations, would not be effective.

If in your son's case one of the two mutations was inherited from the father and the other mutation from the mother, it would be proven molecular genetical basis that he has CF; then he would be compound heterozygous for both mentioned mutations.

From a Swiss paper (3905insT is the second most frequent mutation in Switzerland) of Hergersberg and colleagues (Human Genetics, 1997, 100, 220-223) it is known that 3905insT is a "typical" CF mutation. All referred patients had a pancreatic insufficiency (they needed additional pancreatic enzymes, e.g. Creon). Like in all other "typical" mutations (e.g. F508del, Delta F508) the clinical spectrum is, however, very variable. Therefore, an individual prognosis cannot be given.

Best regards,
Prof. M. Stuhrmann-Spangenberg

22.03.2012