Bowne Sara J, Sullivan Lori S, Avery Cheryl E, Sasser Elizabeth M, Roorda Austin, Duncan Jacque L, Wheaton Dianna H, Birch David G, Branham Kari E, Heckenlively John R, Sieving Paul A, Daiger Stephen P
Human Genetics Center, School of Public Health, The University of Texas Health Science Center Houston, TX.
Mol Vis. 2013 Nov 24;19:2407-17. eCollection 2013.
The purpose of this project was to determine the spectrum and frequency of mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) that cause autosomal dominant retinitis pigmentosa (adRP).
A well-characterized adRP cohort of 251 families was tested for mutations in the exons and intron/exon junctions of SNRNP200 using fluorescent dideoxy sequencing. An additional 21 adRP families from the eyeGENE® Network were tested for possible mutations. Bioinformatic and segregation analysis was performed on novel variants.
SNRNP200 mutations were identified in seven of the families tested. Two previously reported mutations, p.Arg681Cys and p.Ser1087Leu, were found in two families each. One family had the previously reported p.Arg681His mutation. Two novel SNRNP200 variants, p.Pro682Ser and p.Ala542Val, were also identified in one family each. Bioinformatic and segregation analyses suggested that these novel variants are likely to be pathogenic. Clinical examination of patients with SNRNP200 mutations showed a wide range of clinical symptoms and severity, including one instance of non-penetrance.
Mutations in SNRNP200 caused 1.6% of disease in our adRP cohort. Pathogenic mutations were found primarily in exons 16 and 25, but the novel p.Ala542Val mutation in exon 13 suggests that variation in other genetic regions is also responsible for causing dominant disease. SNRNP200 mutations were associated with a wide range of clinical symptoms similar to those of individuals with other splice-factor gene mutations.
本项目旨在确定导致常染色体显性遗传性视网膜色素变性（adRP）的小核核糖核蛋白200 kDa基因（SNRNP200）中的突变谱及频率。
使用荧光双脱氧测序法对251个特征明确的adRP家系进行SNRNP200外显子及内含子/外显子连接区突变检测。另外对来自eyeGENE®网络的21个adRP家系进行可能的突变检测。对新变异进行生物信息学及分离分析。
在检测的家系中有7个家系鉴定出SNRNP200突变。两个先前报道的突变，p.Arg681Cys和p.Ser1087Leu，分别在两个家系中发现。一个家系有先前报道的p.Arg681His突变。两个新的SNRNP200变异，p.Pro682Ser和p.Ala542Val，也分别在一个家系中被鉴定出。生物信息学及分离分析表明这些新变异可能具有致病性。对有SNRNP200突变的患者进行临床检查发现临床症状及严重程度范围广泛，包括一例未外显情况。
在我们的adRP家系队列中，SNRNP200突变导致了1.6%的疾病。致病突变主要发现于外显子16和25，但外显子13中的新p.Ala542Val突变表明其他基因区域的变异也与导致显性疾病有关。SNRNP200突变与一系列广泛的临床症状有关，类似于其他剪接因子基因突变个体的症状。
