Hereditary lymphedema: evidence for linkage and genetic heterogeneity
Hereditary lymphedema: evidence for linkage and genetic heterogeneity
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DOI：
10.1093/hmg/7.13.2073
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发表时间：
1998-12-01
影响因子：
3.5
通讯作者：
Finegold, DN
中科院分区：
文献类型：
--
作者：
Ferrell, RE;Levinson, KL;Finegold, DN
遗传性或原发性淋巴水肿是淋巴系统的一种发育障碍，可导致四肢的致残和毁容肿胀。遗传性淋巴水肿通常表现为常染色体显性遗传模式，外显率降低，表达不同，发病年龄不同。对366个常染色体标记进行基因分型，证明遗传性淋巴水肿分离是一种不完全外显的常染色体显性性状。结果连锁分析显示，标记D5S1354在theta = 0.0处的两点LOD评分为6.1，位于染色体5q34-q35的标记D5S1354的多点LOD评分最高为8.8。使用来自连锁区域的标记对另外两个家族进行连锁分析，发现一个家族与远端5号染色体的连锁一致，在第二个家族中，LOD评分Z < -2.0的区域所有标记都不存在与5q的连锁。血管内皮生长因子C受体（FLT4）被定位到连接区域，部分序列分析在FLT4 cDNA的核苷酸位置3360处发现G- > a过渡，预测在一个核家族中成熟受体的残基1126处亮氨酸取代脯氨酸。本研究将原发性淋巴水肿的基因定位到远端染色体5q，在连锁区域确定了一个可能的候选基因，并为原发性淋巴水肿的第二个非连锁位点提供了证据。
Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. RESULTS Linkage analysis yielded a two-point LOD score of 6.1 at theta = 0.0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5, In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor (FLT4) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.