Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa.
Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa.
复制标题
一个常染色体隐性遗传色素性视网膜炎中国家系中 EYS 中新型纯合无义突变的鉴定
DOI：
10.1186/1471-2350-11-121
复制
发表时间：
2010-08-10
影响因子：
--
通讯作者：
Tang Z
中科院分区：
文献类型：
--
作者：
Huang Y;Zhang J;Li C;Yang G;Liu M;Wang QK;Tang Z
研究背景色素性视网膜炎是最重要的遗传性视网膜退行性疾病，具有高度的临床和遗传异质性。超过一半的色素性视网膜炎病例是常染色体隐性遗传 (arRP)，但在大多数家族中引起 arRP 的基因尚未确定。本研究的目的是明确中国近亲结婚家族中严重arRP的遗传基础。方法采用连锁分析和单倍型分析来确定中国arRP家族中致病基因的染色体位置。对EYS的整个编码区和外显子-内含子边界进行直接DNA序列分析，确定致病突变，并证明该突变与该家族中的疾病共分离。结果在中国arRP家族中，在EYS的5506位核苷酸处发现了G至T的单核苷酸取代。这一变化导致密码子 1,836 处的谷氨酸残基被终止密码子 TAA (p.E1836X) 取代，并导致 EYS 蛋白过早截短，含有 1,835 个氨基酸。家庭中三个受影响的兄弟姐妹是 p.E1836X 突变的纯合子，而其他未受影响的家庭成员携带一个突变等位基因和一个正常的 EYS 等位基因。在200个无关的正常对照中未检测到无义突变p.E1836X。结论EYS基因是最近发现的视网膜色素变性致病基因，编码果蝇spacemaker的直系同源基因。迄今为止，EYS 中只有 8 个突变已被确定会导致 arRP。在这里，我们报告了中国近亲arRP家族中EYS的一种新的纯合无义突变。我们的研究首次独立证实 EY 突变导致 arRP。此外，这是在中国人群中发现的第一个EY突变。
BackgroundRetinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.MethodsLinkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries ofEYSwas used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.ResultsA single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.ConclusionsTheEYSgene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue ofDrosophilaspacemaker. To date, there are only eight mutations inEYSthat have been identified to cause arRP. Here we report one novel homozygous nonsense mutation ofEYSin a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations inEYScause arRP. Additionally, this is the firstEYSmutation identified in the Chinese population.