L227R mutation

Question

Hello,
From a strict physiological point of view, what is the impact of the substitution of Leucine at position 227 to Arginine? Can the different physicochemical properties of those aminoacids explain the dysfunction of the CFTR protein? There is very little documentation about it. Could you enlighten me?

Answer

Hello,
From a biochemical point of view, the change of Leucine aminoacid (hydrophobic) to arginine (basic) results in a physico-chemical modification which may explain the protein dysfunction (it is the case of missense mutations of classes II and III).
From a practical point of view it is difficult to draw reliable conclusions for the evolution of the disease because the L227R mutation is a rare mutation. Indeed, in the French CFTR database, it is reported in 6 CF patients among them 3 are homozygous for this mutation (L227R / L227R). Pancreatic status is known for 3 of the 6 patients and is “pancreatic insufficient”. The CFTR2 international database reports, of over 49,000 registered patients, 9 CF patients carrying a L227R mutation. This number is considered too low to make correlations between genotype (mutations) and phenotype (the evolution of the disease).
Hoping to have answered your question.
Sincerely.
Gilles RAULT, Roscoff CF Center
and
Marie-Pierre AUDREZET, Molecular Genetics Laboratory, Brest University Hospital

03.12.2014