Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): Mapping of locus to chromosome 16 (16q23-qter)
Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): Mapping of locus to chromosome 16 (16q23-qter)
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DOI：
10.1086/302024
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发表时间：
1998-09-01
影响因子：
9.8
通讯作者：
Iolascon, A
中科院分区：
文献类型：
--
作者：
Carella, M;Stewart, G;Iolascon, A
遗传性脱水口红增多症，又称“遗传性干细胞症”，是由红细胞膜缺陷引起的，其特征是口腔性形态，平均红细胞血红蛋白浓度增加，渗透脆性降低，对单价阳离子Na+和K+的通透性增加，以及膜上磷脂酰胆碱的比例增加。临床表现不一，从轻度至中度溶血性贫血合并巩膜黄斑、脾肿大和胆石症不等。铁超载可能会在生命的后期发展。这种疾病是以常染色体显性遗传特征传播的。我们招募了一个受国土安全部影响的三代爱尔兰大家庭，由23名成员组成，其中14人受到影响，9人健康。这项研究还包括另外两个小家庭。来自这些家庭成员的DNA样本用于全基因组搜索，通过连锁分析确定DHS基因座。在排除了人类基因组的一部分后，我们获得了DHS与16号染色体(16q23-q24)长臂上的微卫星标记连锁的确凿证据。标记D16S520在重组分数为0.00时的最大两点LOD得分为6.62。没有重组事件定义该区域的端粒限制，因此端粒限制相当大。没有候选基因映射到这个区域。
Dehydrated hereditary stomatocytosis, also known as "hereditary xerocytosis," is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin concentration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphatidylcholine in the membrane. The clinical presentation is heterogeneous, ranging from mild to moderate hemolytic anemia associated with scleral icterus, splenomegaly, and choletithiasis. Iron overload may develop later in life. The disease is transmitted as an autosomal dominant trait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were healthy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide search to identify, by linkage analysis, the DHS locus. After the exclusion of a portion of the human genome, we obtained conclusive evidence for linkage of DHS to microsatellite markers on the long arm of chromosome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombination fraction .00 was obtained with marker D16S520. There are no recombination events defining the telomeric limit of the region, which therefore is quite large. No candidate genes map to this area.