Mutations in the human laminin beta2 (LAMB2) gene and the associated phenotypic spectrum.
Mutations in the human laminin beta2 (LAMB2) gene and the associated phenotypic spectrum.
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DOI：
10.1002/humu.21304
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发表时间：
2010-09
期刊：
影响因子：
3.9
通讯作者：
Zenker, Martin
中科院分区：
文献类型：
--
作者：
Matejas, Verena;Hinkes, Bernward;Alkandari, Faisal;Al-Gazali, Lihadh;Annexstad, Ellen;Aytac, Mehmet B.;Barrow, Margaret;Blahova, Kveta;Bockenhauer, Detlef;Cheong, Hae Il;Maruniak-Chudek, Iwona;Cochat, Pierre;Doetsch, Joerg;Gajjar, Priya;Hennekam, Raoul C.;Janssen, Francoise;Kagan, Mikhail;Kariminejad, Ariana;Kemper, Markus J.;Koenig, Jens;Kogan, Jillene;Kroes, Hester Y.;Kuwertz-Broeking, Eberhard;Lewanda, Amy F.;Medeira, Ana;Muscheites, Jutta;Niaudet, Patrick;Pierson, Michel;Saggar, Anand;Seaver, Laurie;Suri, Mohnish;Tsygin, Alexey;Wuehl, Elke;Zurowska, Aleksandra;Uebe, Steffen;Hildebrandt, Friedhelm;Antignac, Corinne;Zenker, Martin
LAMB2突变通常会导致常染色体隐性皮尔逊综合征，这是一种以先天性肾病综合征、眼部和神经系统异常为特征的疾病，但偶尔也可能与较轻或少症状的疾病变异相关。LAMB2编码基底膜蛋白层粘连蛋白β2，该蛋白被纳入特异性异源三聚体层粘连蛋白同型中，其表达模式与Pierson综合征的器官表现模式相对应。在这里，我们回顾了所有先前报道的和一些新的LAMB2突变与来自39个不相关家庭的患者的相关表型。大多数致病的LAMB2突变是截短的，这与层粘连蛋白β2功能丧失是Pierson综合征的分子基础的假设是一致的。虽然截断突变分布在整个基因中，但错义突变明显聚集在n端LN结构域，这对分子间相互作用很重要。错义突变和框架内小缺失与肾脏疾病发病平均年龄较高和没有神经系统异常有关，因此表明其中至少有一些可能是次形等位基因。然而，基因型本身似乎不能解释临床变异性的全部范围，因此迄今为止尚未确定的修饰可能存在。
Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2 which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. While truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist.
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影响因子：
64.8
作者：
NOAKES, PG;GAUTAM, M;MERLIE, JP
通讯作者：
MERLIE, JP
影响因子：
3
作者：
Dietrich, Andreas;Matejas, Verena;Zenker, Martin
通讯作者：
Zenker, Martin
层粘连蛋白聚合诱导受体细胞骨架网络。
影响因子：
7.8
作者：
Colognato, H;Winkelmann, D A;Yurchenco, P D
通讯作者：
Yurchenco, P D
影响因子：
4
作者：
Maselli, R. A.;Ng, J. J.;Wollmann, R. L.
通讯作者：
Wollmann, R. L.
影响因子：
8
作者：
Hinkes, Bernward G.;Mucha, Bettina;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm