Infantile steroid-resistant nephrotic syndrome associated with double homozygous mutations of podocin
Infantile steroid-resistant nephrotic syndrome associated with double homozygous mutations of podocin
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DOI：
10.1053/j.ajkd.2003.12.034
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发表时间：
2004-04-01
影响因子：
13.2
通讯作者：
Ghiggeri, GM
中科院分区：
文献类型：
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作者：
Caridi, G;Berdeli, A;Ghiggeri, GM
NPHS2突变，即podocin基因编码，与儿童肾病综合征（NS）有关，其临床表型以发病年龄可变（1至10岁）和类固醇/环孢素耐药性为特征。作者描述了来自土耳其的2个家庭（3例患者）的婴儿变异，其特征是复杂单倍型的纯合性，其中2个podocin突变（P20L-R168H）顺式存在。这是由于在一个更古老的单倍型上插入了一个仅在土耳其发现的新突变（R168H），该单倍型含有在欧洲人群中观察到的P20L突变。所有描述的患者在出生后的前6个月内出现NS，具有严格的药物耐药性和局灶节段性肾小球硬化的组织学背景。这是文献中报道的常染色体隐性肾病双纯合突变的首次描述。与婴儿NS的关联扩大了与NPHS2突变相关的临床表现。
Mutations of NPHS2, ie, the gene coding for podocin, are associated with nephrotic syndrome (NS) in children, with a clinical phenotype characterized by variable age at onset (from 1 to 10 years) and steroid/cyclosporine resistance. The authors describe an infantile variant in 2 families (3 patients) from Turkey, characterized by homozygosity of a complex haplotype, in which 2 podocin mutations (P20L-R168H) are present in cis. It results from the insertion of a new mutation (R168H), only found in Turkey, on a more ancient haplotype containing the P20L mutation observed in the European population. All patients described had presented with NS within the first 6 months of life with strict resistance to drugs and a histologic background of focal segmental glomerulosclerosis. This is the first description of double homozygous mutations in an autosomal recessive renal disease reported in the literature. The association with infantile NS widens the panel of clinical presentation related to NPHS2 mutations.