Mutation spectrum of human SLC39A4 in a panel of patients with acrodermatitis enteropathica.
Acrodermatitis enteropathica is rare autosomal recessive disorder characterized by a severe nutritional zinc deficiency. We and others have recently identified the human gene encoding an intestinal zinc transporter of the ZIP family, SLC39A4, as the mutated gene in acrodermatitis enteropathica (AE). A first mutation screening in 8 AE families (15 patients out of 36 individuals) revealed the presence of six different mutations described elsewhere. Based on these results, we have evaluated the involvement of SLC39A4 in 14 patients of 12 additional AE pedigees coming either from France, Tunisia, Austria or Lithuania. A total of 7 SLC39A4 mutations were identified (1 deletion, 2 nonsense, 2 missense, and 2 modifications of splice site), of which 4 are novel: a homozygous nonsense mutation in 3 consanguineous Tunisian families [c.143T>G (p.Leu48X)], a heterozygous nonsense mutation (c.1203G>A (p.Trp401X)) in a compound heterozygote from Austria also exhibiting an already known missense mutation, and distinct homozygous mutations in families from France or Tunisia [c.475-2A>G and c.184T>C (p.Cys62Arg)]. Furthermore, two other potential mutations [c.850G>A (p.Glu284Lys) and c.193-113T>C] were also observed at homozygous state in a French family formerly described. This study brings to 21 the number of reported SLC39A4 mutations in AE families.
Küry
Sébastien
S
Laboratoire d'Etude du Polymorphisme de l'ADN, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes cedex, France. skury@sante.univ-nantes.fr
Kharfi
Monia
M
Kamoun
Ridha
R
Taïeb
Alain
A
Mallet
Eric
E
Baudon
Jean-Jacques
JJ
Glastre
Catherine
C
Michel
Bruno
B
Sebag
Francis
F
Brooks
David
D
Schuster
Volker
V
Scoul
Catherine
C
Dréno
Brigitte
B
Bézieau
Stéphane
S
Moisan
Jean-Paul
JP
D000169:Acrodermatitis / Q000235:genetics*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry; D015032:Zinc / Q000172:deficiency*
D027682:Cation Transport Proteins; D012333:RNA, Messenger; C486791:SLC39A4 protein, human; D015032:Zinc