Afifi Hanan H, Amr Khalda S, Tosson Angie M S, Hassan Tarak A, Mehrez Mennat I, El-Kamah Ghada Y
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Medical Molecular Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Gene. 2017 Sep 10;628:308-314. doi: 10.1016/j.gene.2017.07.026. Epub 2017 Jul 15.
Lipoid proteinosis (LP) is an autosomal recessive disorder caused by the loss of function of ECM1 gene. Clinical features include varying degrees of skin thickening, hoarseness of voice and less frequently neuropsychiatric abnormalities. Twelve patients from ten unrelated families with a clinical diagnosis of lipoid proteinosis were enrolled in this study. Extraction of DNA samples of the 12 patients and their parents from peripheral blood by standard methods was performed. Polymerase chain reaction (PCR) amplification of the ECM1 gene was conducted using eight pairs of primers spanning over the 10 exons and splice junctions. Patients exhibited a variety of clinical manifestations with skin affection and hoarseness of voice being the consistent feature. We identified five novel homozygous insertion, small deletion, missense, and splice site mutations as well as two homozygous previously published splice site mutation c.70+1G>C in intron 1 and c.1305-2A>G in intron 8. The specific mutations were: c.10_11insC in exon 1, c.690_691delAG in exon 6, c.734G>A in exon 7, c.1286_1287delAA in exon 8 and c.1393-1G>T in intron 9. The novel mutations c.1393-1G>T and c.10_11insC occurred in three (30%) and two (20%) unrelated patients of the studied families, respectively. Further studies may designate an increased frequency of these mutations among Egyptian LP patients. Identification of pathogenic ECM1 mutations is important for accurate diagnosis and proper genetic counseling.
类脂蛋白沉积症（LP）是一种由ECM1基因功能丧失引起的常染色体隐性疾病。临床特征包括不同程度的皮肤增厚、声音嘶哑，较少见的还有神经精神异常。本研究纳入了来自10个无亲缘关系家庭的12例临床诊断为类脂蛋白沉积症的患者。采用标准方法从12例患者及其父母的外周血中提取DNA样本。使用跨越10个外显子和剪接位点的8对引物对ECM1基因进行聚合酶链反应（PCR）扩增。患者表现出多种临床表现，皮肤受累和声音嘶哑是一致的特征。我们鉴定出5种新的纯合插入、小缺失、错义及剪接位点突变，以及2种先前已发表的纯合剪接位点突变，即内含子1中的c.70 + 1G>C和内含子8中的c.1305 - 2A>G。具体突变如下：外显子1中的c.10_11insC、外显子6中的c.690_691delAG、外显子7中的c.734G>A、外显子8中的c.1286_1287delAA以及内含子9中的c.1393 - 1G>T。新突变c.1393 - 1G>T和c.10_11insC分别出现在研究家庭中3例（30%）和2例（20%）无亲缘关系的患者中。进一步研究可能表明这些突变在埃及LP患者中的频率增加。鉴定致病性ECM1突变对于准确诊断和适当的遗传咨询很重要。
