Mutations p.Gly542X and c.371del

Question

Hello,
Our daughter (soon 2½ years) was diagnosed to have CF following a Newborn screening test.
After investigation of the CFTR gene she was diagnosed to be compound heterozygous for mutations p.Gly542X (mutation from her father) and c.371del (mutation from her mother).
What do you know about these 2 mutations? Other carriers of these mutations?
Our daughter seems more sensitive for digestive than for respiratory problems, but so far we can say that she is fine (Pseudomonas 1 time, Staphylococcus 1 time).
Thank you in advance for your answers,
Cordially

Answer

Hello,

the C.371del mutation changes the reading frame and leads to the creation of a stop codon. This is a class I mutation resulting in the absence of CFTR protein synthesis. It is rare and is neither listed in the CFTR-France nor in the US CFTR2 database.

The p.Gly542X mutation commonly referred as G542X is also a class I mutation. It is much more common, found in nearly 3500 patients listed in the CFTR2 database.

These two mutations are mutations called "CF causing" that means they cause cystic fibrosis when associated with another CF causing mutation. Exocrine pancreatic insufficiency is present in 98% of patients with 2 mutations of this type.

Note that the correlations between genotype (mutations) and phenotype (clinical picture) are established statistically for many patients and cannot be applied to a given individual: each clinical evolution is actually unique.

Hope this answer can help.
Best wishes

Gilles RAULT, MD, Roscoff CF Center
With the kind contribution of Ms Marie-Pierre AUDREZET, Genetic Epidemiology, Brest University Hospital

27.02.2016