Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome
Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome
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DOI：
10.1681/asn.2007040452
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发表时间：
2008-02-01
影响因子：
13.6
通讯作者：
Hildebrandt, Friedhelm
中科院分区：
文献类型：
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作者：
Hinkes, Bernward;Vlangos, Christopher;Hildebrandt, Friedhelm
编码podocin（NPHS 2）的基因突变导致常染色体隐性遗传类固醇耐药肾病综合征（SRNS）。为了解决podocin突变和发病年龄之间基因型-表型相关性的可能性，通过直接测序筛选了来自404个不同SRNS家族的430名患者的全球队列。18.1%（73/404）的SRNS家族中存在隐性podocin突变，其中69.9%的突变为无义、移码或纯合R138 Q。这些突变的患者表现出症状在一个显着更早的年龄（平均发病4.17年）。除1例受截短型或纯合型R138 Q突变影响的患者外，所有患者均在6岁之前发生SRNS。其他隐性podocin突变的患者组，与单个杂合podocin突变，与序列变异，并没有podocin变化不能区分彼此的基础上发病年龄。总之，截短型或纯合型R138 Q突变的儿童肾病综合征主要在6岁之前出现，并且疾病的发作明显早于任何其他podocin突变。因为在具有相同突变的患者中，发病年龄可能相差几岁，因此其他因素可能会改变表型。
Mutations in the gene encoding podocin (NPHS2) cause autosomal recessive steroid-resistant nephrotic syndrome (SRNS). For addressing the possibility of a genotype-phenotype correlation between podocin mutations and age of onset, a worldwide cohort of 430 patients from 404 different families with SRNS were screened by direct sequencing. Recessive podocin mutations were present in 18.1% (73 of 404) of families with SRNS, and 69.9% of these mutations were nonsense, frameshift, or homozygous R138Q. Patients with these mutations manifested symptoms at a significantly earlier age (mean onset 4.17 yr). All but one patient affected by truncating or homozygous R138Q mutations developed SRNS before 6 yr of age. Patient groups with other recessive podocin mutations, with single heterozygous podocin mutations, with sequence variants, and with no podocin changes could not be distinguished from each other on the basis of age of onset. In conclusion, nephrotic syndrome in children with truncating or homozygous R138Q mutations manifests predominantly before 6 yr of life, and the onset of disease is significantly earlier than for any other podocin mutations. Because the age of onset can vary by several years among those with identical mutations, additional factors may modify the phenotype.