Mutation spectrum of human SLC39A4 in a panel of patients with acrodermatitis enteropathica.
Mutation spectrum of human SLC39A4 in a panel of patients with acrodermatitis enteropathica.
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DOI：
10.1002/humu.9178
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发表时间：
2003-10-01
期刊：
影响因子：
3.9
通讯作者：
Moisan, Jean-Paul
中科院分区：
文献类型：
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作者：
Kury, Sebastien;Kharfi, Monia;Moisan, Jean-Paul
肠病性肢端皮炎是一种罕见的常染色体隐性遗传疾病，其特征是严重的营养性锌缺乏。我们和其他人最近已经确定了人类基因编码的ZIP家族，SLC 39 A4的肠道锌转运蛋白，突变基因在肢端皮炎肠病（AE）。在8个AE家族（36名个体中的15名患者）中进行的首次突变筛查显示存在其他地方描述的6种不同突变。基于这些结果，我们在来自法国、突尼斯、奥地利或立陶宛的另外12例AE患儿的14例患者中评估了SLC 39 A4的参与。共鉴定出7个SLC 39 A4突变。（1个缺失、2个无义、2个错义和2个剪接位点修饰），其中4个是新的：3个突尼斯血缘家系中的一个纯合无义突变[c.143T>G（p.Leu48X）]，杂合无义突变（c.1203G>A（p.Trp401X）），来自奥地利的复合杂合子也表现出已知的错义突变，在来自法国或突尼斯的家族中存在不同的纯合突变[c.475-2A>G和c.184T>C（p.Cys62Arg）]。此外，在先前描述的一个法国家系中，还观察到另外两个潜在的突变[c.850G>A（p.Glu284Lys）和c.193- 113 T>C]处于纯合状态。这项研究使AE家族中报告的SLC 39 A4突变的数量达到21个。
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.