[Molecular genetics of hemochromatosis].
Haemochromatosis is an inherited disorder of iron metabolism characterized by a general iron over loading. Without diagnosis and early treatment, it is a serious and potentially fatal disease by cardiac failure or hepatocellular carcinoma in particular. Gene prevalence was estimated at 0.06 in Brittany, so that haemochromatosis may be the most common genetic disease in this area. The biochemical defect of the disease is unknown; only one fact is well established: the iron absorption through duodenal mucosa is excessive. However we don't know if it is a primary event. The gene is also unknown but in 1975 it was located on the short arm of chromosome 6, closely linked to the HLA class I region, less than 1 cM from HLA-A. None of the genes coding for the known iron proteins could be the haemochromatosis gene because of their chromosomal localization. In order to locate this gene with precision, we have used a reverse genetic approach now called positional cloning. Characterization of new polymorphic markers and linkage disequilibrium analysis, have led us to locate the gene within a 350 kb region around HLA-A. We have then searched for all the structural genes in this region. Seven new genes have been so identified and located with precision. A structural analysis of these genes was undertaken to find an eventual abnormality in patients.
Le Gall
J Y
JY
Laboratoire de Biochimie Médicale B. Faculté de Médecine, Rennes.
David
V
V
Yaouanq
J
J
Périchon
M
M
Blayau
M
M
Jouanolle
A M
AM
Mauvieux
V
V
el Kahloun
A
A
Chauvel
B
B
Dorval
I
I
D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans
Génétique moléculaire de l'hémochromatose.