THE GENE FOR A HUMAN MICROFIBRIL-ASSOCIATED GLYCOPROTEIN IS COMMONLY DELETED IN SMITH-MAGENIS SYNDROME PATIENTS
THE GENE FOR A HUMAN MICROFIBRIL-ASSOCIATED GLYCOPROTEIN IS COMMONLY DELETED IN SMITH-MAGENIS SYNDROME PATIENTS
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DOI：
10.1093/hmg/4.4.589
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发表时间：
1995-04-01
影响因子：
3.5
通讯作者：
PATEL, PI
中科院分区：
文献类型：
--
作者：
ZHAO, ZY;LEE, CC;PATEL, PI
Smith-Magenis 综合征 (SMS) 是一种临床上可识别的与 17p11.2 染色体缺失相关的多发性先天性异常/智力低下综合征。在这里，我们报告了编码人类微原纤维相关糖蛋白（MFAP4）的新基因的鉴定，该基因已被定位到SMS区域，该基因对应的全长cDNA已被测序，并揭示了255个氨基酸的编码区，MFAP4具有纤维蛋白原样结构域，并且与牛36kDa微原纤维相关糖蛋白的片段具有高度的序列同源性。该蛋白的 N 末端带有 Arg-Gly-Asp 序列，作为细胞表面受体整联蛋白的配体基序。 MFAP4 的这些结构特征表明它是一种参与细胞粘附或细胞间相互作用的细胞外基质蛋白。通过聚合酶链反应和保留 del(17)(p11.2) 染色体的体细胞杂交体 Southern 分析或荧光原位杂交，对 31 名 SMS 患者进行了缺失分析。 31 名 SMS 患者中有 30 名的 MFAP4 基因座被删除。因此，在 SMS 的发病机制中必须考虑该基因的功能。鉴于我们之前的假设，即 SMS 是一种连续基因综合征，需要对关键缺失区间进行完整而详尽的定义，并进行彻底的表型-基因型相关性，以证明 MFAP4 基因在 SMS 中的作用和重要性。
Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. Here we report the identification of a novel gene encoding a human microfibril-associated glycoprotein (MFAP4), which has been mapped to the SMS region, A full-length cDNA corresponding to this gene has been sequenced, and reveals a coding region of 255 amino acids, MFAP4 has a fibrinogen-like domain and shares a high level of sequence homology to a fragment of a bovine 36 kDa microfibril-associated glycoprotein. The N-terminus of the protein bears an Arg-Gly-Asp sequence that serves as the ligand motif for cell surface receptor integrin. These structural features of MFAP4 suggest that it is an extracellular matrix protein involved in cell adhesion or intercellular interactions. Deletion analysis has been conducted on 31 SMS patients by polymerase chain reaction and Southern analysis of somatic cell hybrids retaining the del(17)(p11.2) chromosome or by fluorescence in situ hybridization. The MFAP4 locus is deleted in 30 of 31 SMS patients. Thus, the function of this gene must be considered in the pathogenesis of SMS. Given our previous hypothesis that SMS is a contiguous gene syndrome, complete and exhaustive definition of the critical deletion interval and a thorough phenotype-genotype correlation is required to demonstrate the role and importance of the MFAP4 gene in SMS.