Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13) (q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype
Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13) (q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype
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DOI：
10.1136/jmg.39.12.893
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发表时间：
2002-12-01
影响因子：
4
通讯作者：
Schwartz, CE
中科院分区：
文献类型：
--
作者：
Vervoort, VS;Viljoen, D;Schwartz, CE
1例患有小头畸形、小眼畸形、缺指缺颌症（MMEP）和精神发育迟滞的患者先前报告携带从头倒t（6; 13）（q21;q12）易位。在试图确定假定的致病基因，我们映射的易位断裂点使用荧光原位杂交（FISH）。两个重叠的基因组克隆穿过der（6）染色体上的断裂点，将断裂点区域定位在D 6S 1594和D 6S 1250之间。Southern印迹分析使我们能够确定分选连接蛋白3基因（SNX 3）被破坏。使用反向PCR，我们能够扩增和测序der（6）断裂点区域，其表现出与含有标记D13 S250的BAC克隆的同源性。该克隆使我们能够扩增der（13）断裂点区域并对其进行测序，并确定在任一断裂点处均不存在额外的重排，13号染色体上也没有另一个基因被破坏。因此，易位是平衡的，SNX 3可能是患者MMEP的候选基因。然而，突变筛查dHPLC和Southern印迹分析的另一个散发病例MMEP未能检测到任何点突变或缺失SNX 3编码序列。考虑到位置效应的可能性，der（6）染色体断裂点附近的另一个候选基因可能是原始患者中MMEP的原因，或者同样可能的是，两名患者中的MMEP表型是遗传异质性的结果。
A patient with microcephaly, microphthalmia, ectroclactyly, and prognathism (MMEP) and mental retardation was previously reported to carry a de novo reciprocal t(6; 13)(q21;q12) translocation. In an attempt to identify the presumed causative gene, we mapped the translocation breakpoints using fluorescence in situ hybridisation (FISH). Two overlapping genomic clones crossed the breakpoint on the der(6) chromosome, locating the breakpoint region between D6S1594 and D6S1250. Southern blot analysis allowed us to determine that the sorting nexin 3 gene (SNX3) was disrupted. Using Inverse PCR, we were able to amplify and sequence the der(6) breakpoint region, which exhibited homology to a BAC clone that contained marker D13S250. This clone allowed us to amplify and sequence the der(l 3) breakpoint region and to determine that no additional rearrangement was present at either breakpoint, nor was another gene disrupted on chromosome 13. Therefore, the translocation was balanced and SNX3 is probably the candidate gene for MMEP in the patient. However, mutation screening by dHPLC and Southern blot analysis of another sporadic case with MMEP failed to detect any point mutations or deletions in the SNX3 coding sequence. Considering the possibility of positional effect, another candidate gene in the vicinity of the der(6) chromosome breakpoint may be responsible for MMEP in the original patient or, just as likely, the MMEP phenotype in the two patients results from genetic heterogeneity.