The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy.
The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy.
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DOI：
10.1186/1750-1172-8-16
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发表时间：
2013-01-28
影响因子：
3.7
通讯作者：
Banfi S
中科院分区：
文献类型：
--
作者：
Peluso I;Conte I;Testa F;Dharmalingam G;Pizzo M;Collin RW;Meola N;Barbato S;Mutarelli M;Ziviello C;Barbarulo AM;Nigro V;Melone MA;European Retinal Disease Consortium;Simonelli F;Banfi S
遗传性视网膜营养不良，包括视网膜色素变性和利伯先天性黑蒙等，是一组遗传异质性疾病，导致不同程度的视觉缺陷。它们可以由100多个基因的突变引起，并且有证据表明在相当大比例的患者中存在尚未鉴定的基因。我们的目的是确定一个新的基因的常染色体隐性形式的早发性严重视网膜营养不良的患者携带没有以前描述的突变的已知基因。一个综合的策略，包括纯合性定位和全外显子组测序，以确定负责的突变。在青鳉鱼（Oryzias latipes）模式生物中进行功能测试，以进一步了解ADAMTS18基因在眼和中枢神经系统（CNS）功能障碍中的致病作用。这项研究在分析的患者中发现了ADAMTS18基因的纯合错义突变，该突变最近与Knobloch综合征有关，Knobloch综合征是一种影响眼睛和枕骨颅骨的罕见发育障碍。在青鳉鱼体内进行基因敲除证实了突变具有致病作用，并且该基因的失活对感光细胞功能具有有害影响。这项研究表明，ADAMTS18基因的突变可以导致广泛的眼部疾病表型谱，并有助于进一步阐明视网膜疾病的复杂性。
Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.
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影响因子：
3.9
作者：
Neveling, Kornelia;Collin, Rob W. J.;Gilissen, Christian;van Huet, Ramon A. C.;Visser, Linda;Kwint, Michael P.;Gijsen, Sabine J.;Zonneveld, Marijke N.;Wieskamp, Nienke;de Ligt, Joep;Siemiatkowska, Anna M.;Hoefsloot, Lies H.;Buckley, Michael F.;Kellner, Ulrich;Branham, Kari E.;den Hollander, Anneke I.;Hoischen, Alexander;Hoyng, Carel;Klevering, B. Jeroen;van den Born, L. Ingeborgh;Veltman, Joris A.;Cremers, Frans P. M.;Scheffer, Hans
通讯作者：
Scheffer, Hans
DOI：
10.1073/pnas.0914785107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Conte, Ivan;Carrella, Sabrina;Banfi, Sandro
通讯作者：
Banfi, Sandro
影响因子：
4.6
作者：
Conte, Ivan;Marco-Ferreres, Raquel;Bovolenta, Paola
通讯作者：
Bovolenta, Paola
影响因子：
4.4
作者：
Testa, Francesco;Surace, Enrico Maria;Simonelli, Francesca
通讯作者：
Simonelli, Francesca
影响因子：
12.3
作者：
Wu C;Orozco C;Boyer J;Leglise M;Goodale J;Batalov S;Hodge CL;Haase J;Janes J;Huss JW 3rd;Su AI
通讯作者：
Su AI