Analysis of genes encoding laminin β2 and related proteins in patients with Galloway-Mowat syndrome
Analysis of genes encoding laminin β2 and related proteins in patients with Galloway-Mowat syndrome
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DOI：
10.1007/s00467-008-0880-4
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发表时间：
2008-10-01
影响因子：
3
通讯作者：
Zenker, Martin
中科院分区：
文献类型：
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作者：
Dietrich, Andreas;Matejas, Verena;Zenker, Martin
Gloway-Mowat综合征(GMS)是一种罕见的常染色体隐性遗传病，以早发肾病综合征和小头畸形为特征，并伴有各种中枢神经系统异常。GMS可能代表了一组迄今尚不清楚遗传病因的异质性疾病。临床表型在一定程度上与Pierson综合征(PS)重叠，后者包括先天性肾病综合征和明显的眼部异常，但也可能包括神经发育缺陷和小头畸形。PS是由编码层粘连蛋白β2的基因LAMB2突变引起的。我们假设GMS可能是PS的等位基因，或者是由与层粘连蛋白β2相互作用的蛋白缺陷引起的。因此，在18名GMS或类似GMS表型的患者中，我们分析了编码层粘连蛋白β2(LAMB2)、层粘连蛋白α5(LAMA5)、α3-整合素(ITGA3)、β1-整合素(ITGB1)和α-肌动蛋白-4(ACTN4)的基因，但未能在这些基因中发现导致突变的基因。我们推测LAMA5、ITGA3、ITGB1和ACTN4不直接参与GMS的发病。我们排除了LAMB2作为GMS的候选基因。还需要进一步的研究，包括对GMS家系进行连锁分析，以确定这种疾病的潜在基因。
Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disorder characterized by early onset nephrotic syndrome and microcephaly with various anomalies of the central nervous system. GMS likely represents a heterogeneous group of disorders with hitherto unknown genetic etiology. The clinical phenotype to some extent overlaps that of Pierson syndrome (PS), which comprises congenital nephrotic syndrome and distinct ocular abnormalities but which may also include neurodevelopmental deficits and microcephaly. PS is caused by mutations of LAMB2, the gene encoding laminin beta 2. We hypothesized that GMS might be allelic to PS or be caused by defects in proteins that interact with laminin beta 2. In a cohort of 18 patients with GMS or a GMS-like phenotype we therefore analyzed the genes encoding laminin beta 2 (LAMB2), laminin alpha 5 (LAMA5), alpha 3-integrin (ITGA3), beta 1-integrin (ITGB1) and alpha-actinin-4 (ACTN4), but we failed to find causative mutations in these genes. We inferred that LAMA5, ITGA3, ITGB1, and ACTN4 are not directly involved in the pathogenesis of GMS. We excluded LAMB2 as a candidate gene for GMS. Further studies are required, including linkage analysis in families with GMS to identify genes underlying this disease.