Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.
Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.
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原钙粘着蛋白12的丧失导致双脑脑脑发育不良综合征。
DOI：
10.1002/ana.25327
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发表时间：
2018-11
影响因子：
11.2
通讯作者：
Gleeson JG
中科院分区：
文献类型：
--
作者：
Guemez-Gamboa A;Çağlayan AO;Stanley V;Gregor A;Zaki MS;Saleem SN;Musaev D;McEvoy-Venneri J;Belandres D;Akizu N;Silhavy JL;Schroth J;Rosti RO;Copeland B;Lewis SM;Fang R;Issa MY;Per H;Gumus H;Bayram AK;Kumandas S;Akgumus GT;Erson-Omay EZ;Yasuno K;Bilguvar K;Heimer G;Pillar N;Shomron N;Weissglas-Volkov D;Porat Y;Einhorn Y;Gabriel S;Ben-Zeev B;Gunel M;Gleeson JG
确定常染色体隐性遗传畸形间脑-中脑连接发育不良（DMJD）综合征的病因。对8个DMJD家系进行了全外显子或靶向测序研究，并结合临床和影像学特征进行了详细分析。将患者来源的诱导多能干细胞衍生为神经前体细胞和内皮细胞以研究基因表达。所有患者均显示非成簇原钙粘蛋白-12（PCDH 12）基因的双等位基因突变。其特征性临床表现包括进行性小头畸形、颅面畸形、精神障碍、癫痫和轴性肌张力减退伴不同程度的痉挛。脑成像显示脑干畸形，胼胝体经常变薄，伴有点状脑钙化，反映了PCDH 12在神经和内皮细胞中的表达。这些细胞显示缺乏PCDH 12表达和受损的神经突生长。DMJD患者在PCDH 12中具有双等位基因突变并且缺乏蛋白质表达。这些患者表现为特征性的小头畸形和频繁的异常白色物质束。这种致病性变异预示着脑干畸形和白色物质束缺陷导致的不良结局，应将其添加到与PCDH 12相关疾病相关的表型谱中。
To identify causes of the autosomal recessive malformation diencephalic-mesencephalic junction dysplasia (DMJD) syndrome. Eight families with DMJD were studied by whole exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression. All patients showed bi-allelic mutations in the non-clustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth. DMJD patients have bi-allelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and frequent abnormal white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions.
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影响因子：
14.8
作者：
Levenberg, Shulamit;Ferreira, Lino S.;Chen-Konak, Limor;Kraehenbuehl, Thomas P.;Langer, Robert
通讯作者：
Langer, Robert
影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
11
作者：
Chang H;Hoshina N;Zhang C;Ma Y;Cao H;Wang Y;Wu DD;Bergen SE;Landén M;Hultman CM;Preisig M;Kutalik Z;Castelao E;Grigoroiu-Serbanescu M;Forstner AJ;Strohmaier J;Hecker J;Schulze TG;Müller-Myhsok B;Reif A;Mitchell PB;Martin NG;Schofield PR;Cichon S;Nöthen MM;Swedish Bipolar Study Group;MooDS Bipolar Consortium;Walter H;Erk S;Heinz A;Amin N;van Duijn CM;Meyer-Lindenberg A;Tost H;Xiao X;Yamamoto T;Rietschel M;Li M
通讯作者：
Li M
影响因子：
9.9
作者：
Aran, Adi;Rosenfeld, Nuphar;Levy-Lahad, Ephrat
通讯作者：
Levy-Lahad, Ephrat
影响因子：
3.3
作者：
Biswas S;Emond MR;Duy PQ;Hao le T;Beattie CE;Jontes JD
通讯作者：
Jontes JD