Characterization of a novel gene disrupted by a balanced chromosomal translocation t(2;19)(q11.2;q13.3) in a family with cleft lip and palate
Characterization of a novel gene disrupted by a balanced chromosomal translocation t(2;19)(q11.2;q13.3) in a family with cleft lip and palate
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DOI：
10.1006/geno.1998.5577
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发表时间：
1998-12-01
期刊：
影响因子：
4.4
通讯作者：
Murray, JC
中科院分区：
文献类型：
--
作者：
Yoshiura, K;Machida, J;Murray, JC
唇裂伴或不伴腭裂是一种常见的先天缺陷，遗传上很复杂。使用连锁和候选基因关联研究对非综合征形式进行了遗传研究，仅部分成功地确定了导致口面部裂的基因座。非综合征病例的位点在2p13、4q31、6p24、17q21-q24和19q13.2。最近，我们发现了一个家族，唇腭裂在三代中的两代分离，染色体易位平衡t(2; 19)（q11.2;q13.3）。我们使用位置克隆策略鉴定了一个被19号染色体易位破坏的新基因。在74例不相关的唇腭裂患者的DNA中检测到该基因的8个罕见变异（q < 0.01）和9个常见变异（q > 0.01）；没有变异与唇裂显著相关，这表明该基因不是颅面发育异常的主要因素。该基因CLPTM1在含有成年组织RNA的Northern blots和第10至12天小鼠胚胎的全量原位杂交中普遍表达。CLPTM1编码一种跨膜蛋白，与秀丽隐杆线虫的两个基因具有很强的同源性，提示CLPTM1可能属于一个新的基因家族。(C) 1998学术出版社。
Cleft lip with or without cleft palate is a common birth defect that is genetically complex. The nonsyndromic forms have been studied genetically using linkage and candidate-gene association studies with only partial success in defining the loci responsible for orofacial clefting. Loci for nonsyndromic cases have been suggested on 2p13, 4q31, 6p24, 17q21-q24, and 19q13.2. Recently, we identified a family in which cleft lip and palate segregated in two of three generations with a balanced chromosomal translocation t(2; 19)(q11.2;q13.3). We used a positional-cloning strategy to identify a novel gene disrupted by the translocation on chromosome 19. Eight rare (q < 0.01) and nine common (q > 0.01) variants of this gene were detected in the DNA of 74 unrelated cases of cleft lip and/or cleft palate; no variants associated significantly with clefting, suggesting that this gene is not a major contributor to abnormal craniofacial development. This gene, CLPTM1, was ubiquitously expressed on Northern blots containing RNA from adult tissues and in wholemount in situ hybridization of day 10 to 12 mouse embryos. CLPTM1 encodes a transmembrane protein and has strong homology to two Caenorhabditis elegans genes, suggesting that CLPTM1 may belong to a new gene family. (C) 1998 Academic Press.