Delineation of the clinical, molecular and cellular aspects of novel JAM3 mutations underlying the autosomal recessive hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts.
Delineation of the clinical, molecular and cellular aspects of novel JAM3 mutations underlying the autosomal recessive hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts.
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DOI：
10.1002/humu.22263
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发表时间：
2013-03
期刊：
影响因子：
3.9
通讯作者：
Al-Gazali, Lihadh
中科院分区：
文献类型：
--
作者：
Akawi, Nadia A.;Canpolat, Fuat E.;White, Susan M.;Quilis-Esquerra, Josep;Morales Sanchez, Martin;Jose Gamundi, Maria;Mochida, Ganeshwaran H.;Walsh, Christopher A.;Ali, Bassam R.;Al-Gazali, Lihadh
我们最近发现，大脑的出血性破坏、室管膜下钙化和先天性白内障是由编码连接粘附分子 3 (JAM3) 蛋白的基因的双等位基因突变引起的。来自三个新家庭的受影响成员接受了详细的临床检查，包括大脑成像。受影响的个体呈现出独特的表型，包括大脑出血性破坏、室管膜下钙化和先天性白内障。所有患者都经历了灾难性的临床病程，导致十分之七的患者死亡。对 JAM3 编码外显子进行测序揭示了三个新的纯合突变：c.2T>G (p.M1R)、c.346G>A (p.E116K) 和 c.656G>A (p.C219Y)。 p.M1R 突变影响起始密码子，因此预计会损害蛋白质合成。细胞研究表明，p.C219Y 突变导致突变蛋白在内质网中显着滞留，表明存在运输缺陷。 p.E116K 突变体与野生型一样正常地运输到质膜，并且可能由于缺乏与相互作用伙伴的相互作用而失去了其功能。我们的数据进一步支持 JAM3 在血管系统和大脑的发育和功能中的重要性。
We have recently shown that the hemorrhagic destruction of the brain, subependymal calcification and congenital cataracts is caused by biallelic mutations in the gene encoding junctional adhesion molecule 3 (JAM3) protein. Affected members from three new families underwent detailed clinical examination including imaging of the brain. Affected individuals presented with a distinctive phenotype comprising hemorrhagic destruction of the brain, subependymal calcification and congenital cataracts. All patients had a catastrophic clinical course resulting in death in 7 out of 10 affected individuals. Sequencing the coding exons of JAM3 revealed three novel homozygous mutations: c.2T>G (p.M1R), c.346G>A (p.E116K) and c.656G>A (p.C219Y). The p.M1R mutation affects the start codon and therefore is predicted to impair protein synthesis. Cellular studies showed that the p.C219Y mutation resulted in a significant retention of the mutated protein in the endoplasmic reticulum, suggesting a trafficking defect. The p.E116K mutant traffics normally to the plasma membrane as the wild type and may have lost its function due to the lack of interaction with an interacting partner. Our data further support the importance of JAM3 in the development and function of the vascular system and the brain.
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影响因子：
3.7
作者：
Ali BR;Ben-Rebeh I;John A;Akawi NA;Milhem RM;Al-Shehhi NA;Al-Ameri MM;Al-Shamisi SA;Al-Gazali L
通讯作者：
Al-Gazali L
DOI：
10.1096/fj.11-196220
发表时间：
2012-03
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Colom B;Poitelon Y;Huang W;Woodfin A;Averill S;Del Carro U;Zambroni D;Brain SD;Perretti M;Ahluwalia A;Priestley JV;Chavakis T;Imhof BA;Feltri ML;Nourshargh S
通讯作者：
Nourshargh S
影响因子：
4.8
作者：
Arrate, MP;Rodriguez, JM;Cunningham, SA
通讯作者：
Cunningham, SA
影响因子：
9.8
作者：
Mochida, Ganeshwaran H.;Ganesh, Vijay S.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
3.9
作者：
Lalonde, Emilie;Albrecht, Steffen;Jabado, Nada
通讯作者：
Jabado, Nada