Association of MSX1 and TGFB3 with nonsyndromic clefting in humans
Association of MSX1 and TGFB3 with nonsyndromic clefting in humans
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DOI：
10.1086/301956
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发表时间：
1998-08-01
影响因子：
9.8
通讯作者：
Murray, JC
中科院分区：
文献类型：
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作者：
Lidral, AC;Romitti, PA;Murray, JC
非综合征性唇裂伴或不伴腭裂（CL/P）和仅伴非综合征性腭裂（CPO）是常见的先天性畸形，具有显著的医学、心理、社会和经济后果。CL/ P和CPO都是复杂遗传性状的例子。有足够的证据表明，可以通过候选基因连锁不平衡（LD）策略来识别CL/P和CPO的疾病位点。在以白种人为主的人群中，采用病例对照和核心家庭为基础的方法，筛选了包括TGFA、BCL3、DLX2、MSX1和TGFB3在内的裂裂候选基因，以筛查伴有CL/P或CPO的LD。除了具有阳性家族史的CL/P患者外，先前报道的TGFA合并CL/P和CPO的LD无法得到证实。此外，与先前的研究相反，BCL3与CL/P或CPO之间没有发现LD。CL/P与MSX1和TGFB3以及CPO与MSX1之间存在显著的LD，提示这些基因参与了裂裂的发病机制。此外，在69名CPO患者和一部分CL/P患者中进行了DLX2、MSX1和TGFB3基因的突变搜索。在这些基因的编码区没有发现共同的突变；然而，发现了几种罕见的MSX1和TGFB3变异，可能会改变后者的正常功能。这些结果为未来的研究奠定了基础，包括(a)高加索CL/P患者MSX1和TGFB3基因的突变搜索，以及(b)将CPO患者MSX1突变的搜索扩展到非编码区。
Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/ P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions.