Mal de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates
Mal de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates
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DOI：
10.1007/s00439-002-0838-8
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发表时间：
2003-01-01
期刊：
影响因子：
5.3
通讯作者：
Hennies, HC
中科院分区：
文献类型：
--
作者：
Eckl, KM;Stevens, HP;Hennies, HC
Mal de Meleda（MDM）或Siemens的transgrediens掌跖角化病是一种常染色体隐性皮肤病，其特征为弥漫性掌跖角化病（PPK）和越界角化病，在婴儿早期发病。没有相关的其他器官的参与，但是，一系列的临床表现与可选的和可变的功能已被描述。最近在MDM患者中发现了编码SLURP-1的染色体8 q24-qter上ARS（组分B）-81/s基因（LY 6 LS）的突变。在这里，我们分析了四个MDM家族的SLURP-1突变。在一个具有多个血缘关系的大型巴勒斯坦家系中，患者是一个新突变的纯合子，该突变在位置86处用精氨酸取代保守的甘氨酸残基。土耳其患者的不同突变导致相同的氨基酸交换。在两个家庭的患者的临床表现中可以看到一些显着的相似之处。阿联酋贝都因家族的患者具有翻译起始密码子的纯合改变。在一个没有血缘关系的德国家庭中，我们发现了假显性遗传。三个受影响的儿童和他们受影响的母亲是纯合子的错义突变W15 R。我们的研究结果表明，MDM型的越界PPK是由SLURP-1突变引起的患者来自不同的起源和SLURP-1突变的等位基因异质性。
Mal de Meleda (MDM) or keratosis palmoplantaris transgrediens of Siemens is an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma (PPK) and transgressive keratosis with an onset in early infancy. There is no associated involvement of other organs; however, a spectrum of clinical presentations with optional and variable features has been described. Mutations in the ARS (component B)-81/s gene (LY6LS) on chromosome 8q24-qter, which encodes SLURP-1, have recently been identified in patients with MDM. Here, we have analyzed four MDM families for mutations in SLURP-1. In a large Palestinian pedigree with multiple consanguinity, patients are homozygous for a new mutation that substitutes an arginine for a conserved glycine residue at position 86. A different mutation in Turkish patients results in the same amino acid exchange. Some remarkable similarities are seen in the clinical picture of patients from both families. Patients of an Emirati Bedouin family have a homozygous alteration of the translation initiation codon. In a German family with no known consanguinity, we have shown pseudodominant inheritance. Three affected children and their affected mother are homozygous for the missense mutation W15R. Our findings indicate that the MDM type of transgressive PPK is caused by SLURP-1 mutations in patients from various origins and demonstrate allelic heterogeneity for mutations in SLURP-1.