Novel GUCA1A mutations suggesting possible mechanisms of pathogenesis in cone, cone-rod, and macular dystrophy patients.
Novel GUCA1A mutations suggesting possible mechanisms of pathogenesis in cone, cone-rod, and macular dystrophy patients.
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DOI：
10.1155/2013/517570
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发表时间：
2013
影响因子：
--
通讯作者：
Bhattacharya SS
中科院分区：
文献类型：
--
作者：
Kamenarova K;Corton M;García-Sandoval B;Fernández-San Jose P;Panchev V;Avila-Fernández A;López-Molina MI;Chakarova C;Ayuso C;Bhattacharya SS
在这里，我们报告了两个新的GUCA 1A（鸟苷酸环化酶激活蛋白1基因）突变，在不相关的西班牙家庭受常染色体显性视网膜变性（adRD）与锥和杆参与。来自三代adRD谱系的所有患者都接受了详细的眼科评估。对家系进行单核苷酸多态性全基因组扫描和连锁分析。单倍型分析显示，55.37 Mb的基因组间隔与染色体6p21.31-q15上的疾病表型共分离。位置候选基因的突变筛查发现GUCA 1A外显子4中的杂合转换c.250C>T，对应于新突变p.L84F。第二个错义突变，c.320T>C（p.I107T），是通过在西班牙患者队列中筛选该基因而检测到的。利用生物信息学的方法，我们预测了c.250C>T和c.320T>C的致病机制可能是单倍不足或显性-负效应伴随着突变蛋白新功能的产生。尽管还需要进行额外的功能研究，但我们关于c.250C>T突变的数据表明，反式作用因子与从头产生的识别位点结合，导致形成异常剪接变体，这可能是一种比以前认为的导致遗传性RD的机制更为广泛的疾病模型。
Here, we report two novel GUCA1A (the gene for guanylate cyclase activating protein 1) mutations identified in unrelated Spanish families affected by autosomal dominant retinal degeneration (adRD) with cone and rod involvement. All patients from a three-generation adRD pedigree underwent detailed ophthalmic evaluation. Total genome scan using single-nucleotide polymorphisms and then the linkage analysis were undertaken on the pedigree. Haplotype analysis revealed a 55.37 Mb genomic interval cosegregating with the disease phenotype on chromosome 6p21.31-q15. Mutation screening of positional candidate genes found a heterozygous transition c.250C>T in exon 4 of GUCA1A, corresponding to a novel mutation p.L84F. A second missense mutation, c.320T>C (p.I107T), was detected by screening of the gene in a Spanish patients cohort. Using bioinformatics approach, we predicted that either haploinsufficiency or dominant-negative effect accompanied by creation of a novel function for the mutant protein is a possible mechanism of the disease due to c.250C>T and c.320T>C. Although additional functional studies are required, our data in relation to the c.250C>T mutation open the possibility that transacting factors binding to de novo created recognition site resulting in formation of aberrant splicing variant is a disease model which may be more widespread than previously recognized as a mechanism causing inherited RD.
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影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
3
作者：
Faraggi, Eshel;Zhang, Tuo;Yang, Yuedong;Kurgan, Lukasz;Zhou, Yaoqi
通讯作者：
Zhou, Yaoqi
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
4.4
作者：
Johnson, S;Halford, S;Hunt, DM
通讯作者：
Hunt, DM
影响因子：
3.9
作者：
Homolova, Katerina;Zavadakova, Petra;Doktor, Thomas Koed;Schroeder, Lisbeth Dahl;Kozich, Viktor;Andresen, Brage S.
通讯作者：
Andresen, Brage S.