Identification of the gene for Nance-Horan syndrome (NHS)
Identification of the gene for Nance-Horan syndrome (NHS)
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DOI：
10.1136/jmg.2004.022517
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发表时间：
2004-10-01
影响因子：
4
通讯作者：
Hardcastle, AJ
中科院分区：
文献类型：
--
作者：
Brooks, SP;Ebenezer, ND;Hardcastle, AJ
背景资料：Nance-Horan综合征（NHS [MIM 302350]）和X连锁先天性白内障（CXN）的发病间隔在Xp 22上重叠。目的：寻找与这两种疾病相关的基因。CXN基因的精确位点被用来集中寻找候选基因，这些候选基因通过聚合酶链反应和潜在外显子和内含子-外显子剪接位点的直接测序来筛选。使用生物信息学确定基因组结构和同源性。表达研究进行了使用特定的外显子引物扩增人胎儿cDNA和小鼠RNA.Results：一个新的基因NHS，没有已知的功能，被确定为致病NHS。在所有三个NHS家系中均检测到蛋白质截短突变，但在CXN家族中未发现突变，这增加了NHS和CXN可能不是等位基因的可能性。NHS基因与一个新基因NHS-Like 1（NHSL 1）形成一个新的基因家族。NHS和NHSL 1位于Xp 22和6 q24上的旁系同源重复染色体间隔，NHSL 1在人胎儿tissues.Conclusions中的表达比NHS更广泛：本研究报告了Nance-Horan综合征致病基因的独立鉴定，并扩展了鉴定的突变数量。
Background: The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and X linked congenital cataract (CXN) overlap on Xp22.Objective: To identify the gene or genes responsible for these diseases.Methods: Families with NHS were ascertained. The refined locus for CXN was used to focus the search for candidate genes, which were screened by polymerase chain reaction and direct sequencing of potential exons and intron-exon splice sites. Genomic structures and homologies were determined using bioinformatics. Expression studies were undertaken using specific exonic primers to amplify human fetal cDNA and mouse RNA.Results: A novel gene NHS, with no known function, was identified as causative for NHS. Protein truncating mutations were detected in all three NHS pedigrees, but no mutation was identified in a CXN family, raising the possibility that NHS and CXN may not be allelic. The NHS gene forms a new gene family with a closely related novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than NHS in human fetal tissues.Conclusions: This study reports the independent identification of the gene causative for Nance-Horan syndrome and extends the number of mutations identified.