17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)
17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)
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DOI：
10.1038/ejhg.2011.97
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发表时间：
2011-11-01
影响因子：
5.2
通讯作者：
Graham, Gail E.
中科院分区：
文献类型：
--
作者：
Armour, Christine M.;Bulman, Dennis E.;Graham, Gail E.
手足分裂畸形伴长骨缺乏症是一种相对罕见的常染色体显性遗传性骨骼疾病，其特点是表现力不稳定和外显不完全。尽管已确定了SHFLD的几个染色体位点，但大多数SHFLD的分子基础和发病机制尚不清楚。在这项研究中，我们描述了三个不相关的家系，其中SHFLD分离，在17p13.3有不同但重叠的重复，这是一个以前与SHFLD连锁的区域。在一个三代人的大家庭中，发现该疾病以254kb的微复制分离；在一名患病女性及其未患病的母亲中发现了第二个527kb的微复制；在一个多代家庭的三名受影响成员中发现了430kb的微复制与微三重。这些发现和以前发表的数据一起表明，导致这种形式的SHFLD的一个基因座位于173kb的重叠临界区内，复制收益是不完全穿透的。《欧洲人类遗传学杂志》(2011年)1911441151；DOI：10.1038/ejhg.2011.97；2011年6月1日在线发布
Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.3, a region previously linked to SHFLD. In a large three-generation family, the disorder was found to segregate with a 254 kb microduplication; a second microduplication of 527 kb was identified in an affected female and her unaffected mother, and a 430 kb microduplication versus microtriplication was identified in three affected members of a multi-generational family. These findings, along with previously published data, suggest that one locus responsible for this form of SHFLD is located within a 173 kb overlapping critical region, and that the copy gains are incompletely penetrant. European Journal of Human Genetics (2011) 19, 1144-1151; doi: 10.1038/ejhg.2011.97; published online 1 June 2011