PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.
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DOI：
10.1093/brain/awx014
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Baple EL
中科院分区：
文献类型：
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作者：
Zollo M;Ahmed M;Ferrucci V;Salpietro V;Asadzadeh F;Carotenuto M;Maroofian R;Al-Amri A;Singh R;Scognamiglio I;Mojarrad M;Musella L;Duilio A;Di Somma A;Karaca E;Rajab A;Al-Khayat A;Mohan Mohapatra T;Eslahi A;Ashrafzadeh F;Rawlins LE;Prasad R;Gupta R;Kumari P;Srivastava M;Cozzolino F;Kumar Rai S;Monti M;Harlalka GV;Simpson MA;Rich P;Al-Salmi F;Patton MA;Chioza BA;Efthymiou S;Granata F;Di Rosa G;Wiethoff S;Borgione E;Scuderi C;Mankad K;Hanna MG;Pucci P;Houlden H;Lupski JR;Crosby AH;Baple EL
Zollo等人报道，在来自阿曼、印度、伊朗和意大利的四个不相关家族中，磷酸酯酶超家族分子PRUNE 1的突变是原发性小头畸形和严重的整体发育迟缓的基础。这项研究强调了prune在微管聚合过程中的潜在作用，表明prune综合征可能是一种微管蛋白病。PRUNE是DHH（Asp-His-His）磷酸酯酶蛋白超家族的成员，其分子对细胞运动性很重要，并与癌症进展有关。在这里，我们调查了来自阿曼，印度，伊朗和意大利的多个家庭与个人受到一种新的常染色体隐性遗传神经发育和退行性疾病，其中的主要特点包括原发性小头畸形和深刻的全球发展迟缓。我们的遗传学研究确定了PRUNE 1的双等位基因突变负责。我们对疾病相关的变异等位基因的功能测定显示，突变体PRUNE的微管聚合以及细胞迁移和增殖特性受损。此外，我们的研究还强调了PRUNE在微管聚合过程中的潜在新作用，这对于细胞分裂和增殖过程中发生的细胞骨架重排至关重要。这些研究共同将PRUNE定义为正常人类皮质发育的基础分子，并定义了与PRUNE突变相关的细胞和临床后果。
Zollo et al. report that mutations in PRUNE1, a phosphoesterase superfamily molecule, underlie primary microcephaly and profound global developmental delay in four unrelated families from Oman, India, Iran and Italy. The study highlights a potential role for prune during microtubule polymerization, suggesting that prune syndrome may be a tubulinopathy. PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.