Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome
Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome
复制标题
DOI：
10.1086/510919
复制
发表时间：
2007-02-01
影响因子：
9.8
通讯作者：
Mundlos, Stefan
中科院分区：
文献类型：
--
作者：
Klopocki, Eva;Schulze, Harald;Mundlos, Stefan
血小板减少性桡骨缺如（TAR）综合征的特征是少巨核细胞性血小板减少症和双侧桡骨发育不全，同时伴有两个拇指。其他常见的关联是先天性心脏病和牛奶不耐受的高发病率。常染色体隐性遗传的证据来自于有几个受影响的个体出生于未受影响的父母的家庭，但其他一些观察结果表明遗传模式更复杂。在这项研究中，我们描述了一个共同的间质微缺失200 kb的染色体1q21.1在所有30例TAR综合征患者，检测基于微阵列的比较基因组杂交。对父母的分析显示，这种缺失在25%的受影响个体中从头发生。有趣的是，观察到缺失沿着母系以及父系遗传。在对照个体队列中没有这种缺失，这表明微缺失在TAR综合征的发病机制中发挥了特定作用。我们假设TAR综合征与染色体1q21.1上的缺失相关，但表型仅在存在额外的未知修饰物（mTAR）的情况下才发生。
Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow's milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR).