A next-generation sequencing-based strategy of searching for disease genes that are indispensable for viability of glomerular podocytes and peripheral neurons

外周神经元和肾小球足细胞是终末分化的细胞，易受损伤，与神经元和肾脏疾病的发生密切相关，阐明这些非再生细胞生存所需的共同生物学途径将为更好地理解周围神经病和局灶节段性肾小球硬化（FSGS）的机制提供线索我们利用新一代测序技术对FSGS和Charcot-Marie-Tooth型DIE患者的疾病基因进行了研究。结果表明，这些患者是INF 2错义突变的杂合子，这些突变聚集在靠近N-末端的位置。与仅显示FSGS的单一疾病患者的报告相比，使用培养细胞的表达研究正在进行中，以研究除了足细胞的损失之外，突变如何引起神经元变性。

Peripheral neurons and glomerular podocytes are terminally differentiated cells.They are therefore susceptible to injury and associated with the occurrence of neuronal and kidney diseases.Elucidation of common biological pathway needed for these non-regenerating cells to survive will provide clues for better understanding of mechanisms underlying peripheral neuropathy and focal segmental glomerulosclerosis(FSGS).We here explored the disease genes of patients exhibiting both FSGS and Charcot-Marie-Tooth type DIE by next-generation sequencing.The results demonstrated that the patients were heterozygotes for missense mutations in inverted formin-2(INF2).These mutations were clustered in a position closer to N-terminus in compared with those reported in patients with a single disease showing FSGS alone. Expression study using culture cell is now underway to investigate how the mutations could give rise to neuron degeneration in addition to loss of podocytes.