小说FLT4错义突变导致常染色体隐性遗传性淋巴水肿。
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Melikhan-Revzin年代,Kurolap,达冈E,酒吧,Gershoni-Baruch R
小说FLT4错义突变导致常染色体隐性遗传性淋巴水肿。
Lymphat Res杂志。2015年6月,13 (2):107 - 11。doi: 10.1089 / lrb.2014.0044。Epub 2015 6月2。
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26091405 (在PubMed]
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背景:原发性淋巴水肿覆盖所有淋巴水肿病例的10%左右。大多数情况下隔离作为常染色体显性特征,很少体现常染色体隐性遗传。我们的研究旨必威国际app在并最终映射到狩猎的突变引起的遗传性淋巴水肿延长血缘的穆斯林家庭组成的几个影响个人。分子诊断方法和结果:我们试图通过应用纯合性映射和全基因组关联分析。候选轨迹的2.3 Mb位于5号染色体q35.3被确认,产生一个总体LOD得分为3.18。这个轨迹曾经与先天性淋巴水肿,即由FLT4基因。突变FLT4以前描述的Muslim-Israeli家庭使用序列分析被丢弃的罪魁祸首。Sanger测序揭示小说错义变体基因外显子28 (NM_182925.4: c.3704C > G;p.Ser1235Cys)。这变种已经完美的种族隔离在大家庭和不是常见或致病性变异之前报道的数据库。 CONCLUSIONS: Our mutation is the first reported pathogenic variant located outside the tyrosine kinase domains of the VEGFR3 receptor, and the second to portray autosomal recessive inheritance. The homozygous substitution of serine by cysteine at position 1235 affects protein tyrosine kinase activity, possibly through a null effect mechanism rather than a negative dominant effect. Our variant is associated with a mild phenotype, possibly reflecting some residual receptor activity, most probably attributed to the variant's location beyond the TK domains.