Aucella F, Bisceglia L, Stallone C
Divisione di Nefrologia e Dialisi, Ospedale "Casa Sollievo della Sofferenza", Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo (FG), Italy.
G Ital Nefrol. 2003 Jul-Aug;20(4):356-67.
Recent studies of Mendelian disease have begun to clarify the clinical spectrum of the group of disorders that make up familial, focal segmental glomerulosclerosis (FSGS) and nephrotic syndromes. In familial forms of focal segmental glomerulosclerosis (FSGS), both autosomal recessive and dominant inheritance patterns have been reported. At least three genes have been identified which, when defective, cause familial FSGS or nephrosis: the NPHS1 gene, encoding nephrin; the NPHS2 gene, encoding podocin; and the ACTN4 gene, encoding a-actinin-4. Because the majority of FSGS cases occur as sporadic disease, the recently described mutations in the NPHS2 gene "in approximately 25 percent of cases of apparently sporadic, steroid-resistant FSGS in children" have claimed great interest. The applicability of these observations to adults, including the possible importance of the nephrin and alpha-actinin-4 genes in the sporadic disease, remain to be determined. Finally, the mechanisms of podocyte damage and the molecular basis of glomerulosclerosis are reviewed.
近期对孟德尔疾病的研究已开始阐明构成家族性局灶节段性肾小球硬化（FSGS）和肾病综合征的一组疾病的临床谱。在家族性局灶节段性肾小球硬化（FSGS）中，已报道了常染色体隐性和显性遗传模式。至少已鉴定出三个基因，这些基因发生缺陷时会导致家族性FSGS或肾病：编码nephrin的NPHS1基因；编码podocin的NPHS2基因；以及编码α-辅肌动蛋白-4的ACTN4基因。由于大多数FSGS病例表现为散发性疾病，因此最近在NPHS2基因中描述的突变（“在大约25%的明显散发性、类固醇抵抗性儿童FSGS病例中”）引起了极大关注。这些观察结果对成年人的适用性，包括nephrin和α-辅肌动蛋白-4基因在散发性疾病中的可能重要性，仍有待确定。最后，对足细胞损伤机制和肾小球硬化的分子基础进行了综述。
