Dietrich Andreas, Matejas Verena, Bitzan Martin, Hashmi Seema, Kiraly-Borri Cathy, Lin Shuan-Pei, Mildenberger Eva, Hoppe Bernd, Palm Lars, Shiihara Takashi, Steiss Jens-Oliver, Tsai Jeng-Daw, Vester Udo, Weber Stefanie, Wühl Elke, Zepf Kristina, Zenker Martin
Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054, Erlangen, Germany.
Pediatr Nephrol. 2008 Oct;23(10):1779-86. doi: 10.1007/s00467-008-0880-4. Epub 2008 Jul 2.
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 beta2. We hypothesized that GMS might be allelic to PS or be caused by defects in proteins that interact with laminin beta2. In a cohort of 18 patients with GMS or a GMS-like phenotype we therefore analyzed the genes encoding laminin beta2 (LAMB2), laminin alpha5 (LAMA5), alpha3-integrin (ITGA3), beta1-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.
加洛韦 - 莫瓦特综合征（GMS）是一种罕见的常染色体隐性疾病，其特征为早发性肾病综合征和小头畸形，并伴有各种中枢神经系统异常。GMS可能代表一组病因不明的异质性疾病。其临床表型在一定程度上与皮尔森综合征（PS）重叠，PS包括先天性肾病综合征和独特的眼部异常，但也可能包括神经发育缺陷和小头畸形。PS由编码层粘连蛋白β2的基因LAMB2突变引起。我们推测GMS可能与PS等位，或者由与层粘连蛋白β2相互作用的蛋白质缺陷引起。因此，在一组18例患有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 - 辅肌动蛋白 - 4（ACTN4）的基因，但未在这些基因中发现致病突变。我们推断LAMA5、ITGA3、ITGB1和ACTN4不直接参与GMS的发病机制。我们排除了LAMB2作为GMS的候选基因。需要进一步研究，包括对GMS家系进行连锁分析以确定该疾病的潜在基因。
