Molecular basis of lipoid proteinosis in a Libyan family
Molecular basis of lipoid proteinosis in a Libyan family
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DOI：
10.1046/j.1365-2230.2003.01341.x
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发表时间：
2003-09-01
影响因子：
4.1
通讯作者：
McGrath, JA
中科院分区：
文献类型：
--
作者：
Chan, I;El-Zurghany, A;McGrath, JA
类脂质蛋白沉积症是一种常染色体隐性遗传疾病，与皮肤和粘膜的瘢痕形成和浸润有关。该疾病最近被证明是由细胞外基质蛋白1基因（ECM 1）1q21上的功能缺失突变引起的。细胞外基质蛋白1在表皮分化、真皮胶原和蛋白多糖结合、血管生成调控等方面具有重要的生理和生物学作用。迄今为止，在全世界16个不同的类脂质蛋白沉积症家族中描述了致病性突变。在这份报告中，我们描述了一个10岁的男孩与类脂质蛋白沉积症的临床病理特征，从一个血缘关系的利比亚家庭。通过对受影响个体的基因组DNA进行直接测序，我们在ECM 1基因的外显子2中鉴定了一个纯合无义突变Q32X。该突变是迄今为止描述的所有ECM 1突变中最靠近5'端的突变，预计会消除ECM 1基因的ECM 1a、ECM 1b和ECM 1c剪接变体，并导致严重的临床表型。对受影响个体的五个兄弟姐妹的DNA测序显示，其中四个是Q32X杂合子携带者，鉴于利比亚近亲婚姻的频率很高，这一发现对遗传咨询具有重要意义。
Lipoid proteinosis is an autosomal recessive condition associated with variable scarring and infiltration of skin and mucosae. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1) on 1q21. Extracellular matrix protein 1 has important physiological and biological roles in aspects of epidermal differentiation, binding of dermal collagens and proteoglycans, and in regulation of angiogenesis. Thus far pathogenic mutations have been described in 16 different families with lipoid proteinosis throughout the world. In this report, we describe the clinico-pathological features of a 10-year-old boy with lipoid proteinosis from a consanguineous Libyan family. By direct sequencing of the affected individual's genomic DNA, we identified a homozygous nonsense mutation in exon 2 of the ECM1 gene, Q32X. This mutation is the most 5' of all ECM1 mutations described thus far and is predicted to ablate the ECM1a, ECM1b and ECM1c splice variants of the ECM1 gene and to result in a severe clinical phenotype. Sequencing of DNA from the affected individual's five siblings revealed that four were heterozygous carriers of Q32X, findings that have important implications for genetic counselling given the high frequency of consanguineous marriages in Libya.