Mapping of both autosomal recessive and dominant variants of pseudoxanthoma elasticum to chromosome 16p13.1.
Mapping of both autosomal recessive and dominant variants of pseudoxanthoma elasticum to chromosome 16p13.1.
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DOI：
10.1093/hmg/6.11.1823
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发表时间：
1997-10
影响因子：
3.5
通讯作者：
B. Struk;B. Struk;Kenneth H. Neldner;Valluri S. Rao;Valluri S. Rao;Pamela St. Jean;Klaus Lindpaintner
中科院分区：
文献类型：
--
作者：
B. Struk;B. Struk;Kenneth H. Neldner;Valluri S. Rao;Valluri S. Rao;Pamela St. Jean;Klaus Lindpaintner
弹性假性黄瘤（PXE）是一种典型的弹性组织遗传性疾病，以弹性纤维进行性钙化为特征，具有病理组织学表现。PXE的临床表现通常累及皮肤、眼睛和心血管系统，导致皮肤病变、视力下降和血管疾病。临床上，更常见的常染色体隐性遗传模式和不太常见的常染色体显性遗传模式，具有高外显率，已被描述；该疾病的估计患病率为7万至10万分之一。先前未能将该疾病与几个候选基因中的任何一个联系起来，促使我们对38个有两个或更多患病兄弟姐妹的家庭进行全基因组筛选，使用等位基因共享算法。在16号染色体短臂上发现过多的等位基因共享，经常规连锁分析证实，将疾病基因定位在隐性模式下，在16p13.1染色体上最大两点负载评分为21.27，目前尚无明显的候选基因。在优势传播模式下，同一区域的最大2点负荷得分为14.53。连锁异质性分析预测存在等位基因异质性，存在于该染色体区域的单个基因的不同变体，解释了隐性和显性形式的PXE。
Pseudoxanthoma elasticum (PXE) is a classic inherited disorder of the elastic tissue characterized by progressive calcification of elastic fibers with a pathognomonic histological appearance. The clinical manifestations of PXE typically involve the skin, the eye and the cardiovascular system, resulting in skin lesions, decreased vision and vascular disease. Clinically, a more common autosomal recessive and a less common autosomal dominant pattern of inheritance, with high penetrance, have been described; the estimated prevalence of the disease is 1 in 70,000-100,000. Previous failure to link the disease to any of several candidate genes prompted us to conduct a genome-wide screen on a collection of 38 families with two or more affected siblings, using allele sharing algorithms. Excess allele sharing was found on the short arm of chromosome 16 and confirmed by conventional linkage analysis, localizing the disease gene under a recessive model with a maximum two point lod score of 21.27 on chromosome 16p13.1, an area so far devoid of any obvious candidate genes. Under a dominant transmission pattern linkage with a maximum two point lod score of 14.53 was observed to the same region. Linkage heterogeneity analysis predicted the presence of allelic heterogeneity with different variants of a single gene that resides in this chromosomal region accounting for recessive and dominant forms of PXE.