Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa
Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa
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DOI：
10.1542/peds.2005-0160
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发表时间：
2005-10-01
期刊：
影响因子：
8
通讯作者：
Miyazaki, K
中科院分区：
文献类型：
--
作者：
Hata, D;Miyazaki, M;Miyazaki, K
赫利茨交界性大疱性表皮松解症 (H-JEB) 是一种遗传性大疱性疾病，由层粘连蛋白 5 表达缺失引起，层粘连蛋白 5 是真皮-表皮基底膜区域内锚定细丝的组成部分。受影响的个体通常在生命的头一年内死亡。我们研究了一名患有 H-JEB 的婴儿，该婴儿出现肾病综合征，这是一种以前未报告的并发症，可能导致该疾病过早死亡。 DNA 分析揭示了 LAMB3 基因中 2379delG 和 Q995X 突变的复合杂合子。该患者因肾小球滤过屏障失效而出现大量蛋白尿，尿中 N-乙酰氨基葡萄糖苷酶水平较高，表明肾小管受累。肾组织的电子显微镜检查显示足突弥漫性融合、内板内板不规则肿胀以及内皮细胞开窗消失。对患者肾组织的免疫组织病理学分析显示，肾小球基底膜层粘连蛋白亚型的成分发生变化，并且肾小管基底膜中未检测到层粘连蛋白-5，这表明层粘连蛋白-5可能在肾功能中发挥重要作用。我们的研究结果强烈表明，H-JEB 应纳入先天性肾病综合征的范畴。针对先天性肾病综合征建立的细致皮肤护理和治疗策略的联合治疗可能会挽救这种疾病的患者。
Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient's renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.