title: Mutation spectrum of human SLC39A4 in a panel of patients with acrodermatitis enteropathica.
abstract: 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.
authors.affiliation: Laboratoire d'Etude du Polymorphisme de l'ADN, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes cedex, France. skury@sante.univ-nantes.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.forename: Monia
authors.initials: M
authors.lastname: Kharfi
authors.forename: Ridha
authors.initials: R
authors.lastname: Kamoun
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
authors.forename: Eric
authors.initials: E
authors.lastname: Mallet
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Baudon
authors.forename: Catherine
authors.initials: C
authors.lastname: Glastre
authors.forename: Bruno
authors.initials: B
authors.lastname: Michel
authors.forename: Francis
authors.initials: F
authors.lastname: Sebag
authors.forename: David
authors.initials: D
authors.lastname: Brooks
authors.forename: Volker
authors.initials: V
authors.lastname: Schuster
authors.forename: Catherine
authors.initials: C
authors.lastname: Scoul
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Moisan
mesh_terms: 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*
chemical_list: D027682:Cation Transport Proteins; D012333:RNA, Messenger; C486791:SLC39A4 protein, human; D015032:Zinc