Περίληψη:
Juvenile hemochromatosis is an early-onset autosomal recessive disorder
of iron overload resulting in cardiomyopathy, diabetes and hypogonadism
that presents in the teens and early 20s (refs. 1,2). Juvenile
hemochromatosis has previously been linked to the centromeric region of
chromosome 1q (refs. 3 6), a region that is incomplete in the human
genome assembly. Here we report the positional cloning of the locus
associated with juvenile hemochromatosis and the identification of a new
gene crucial to iron metabolism. We finely mapped the recombinant
interval in families of Greek descent and identified multiple
deleterious mutations in a transcription unit of previously unknown
function (LOC148738), now called HFE2, whose protein product we call
hemojuvelin. Analysis of Greek, Canadian and French families indicated
that one mutation, the amino acid substitution G320V, was observed in
all three populations and accounted for two-thirds of the mutations
found. HFE2 transcript expression was restricted to liver, heart and
skeletal muscle, similar to that of hepcidin, a key protein implicated
in iron metabolism(7-9). Urinary hepcidin levels were depressed in
individuals with juvenile hemochromatosis, suggesting that hemojuvelin
is probably not the hepcidin receptor. Rather, HFE2 seems to modulate
hepcidin expression.
Συγγραφείς:
Papanikolaou, G
Samuels, ME
Ludwig, EH
MacDonald, MLE and
Franchini, PL
Dube, MP
Andres, L
MacFarlane, J and
Sakellaropoulos, N
Politou, M
Nemeth, E
Thompson, J and
Risler, JK
Zaborowska, C
Babakaiff, R
Radomski, CC
Pape,
TD
Davidas, O
Christakis, J
Brissot, P
Lockitch, G and
Ganz, T
Hayden, MR
Goldberg, YP
