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细胞。因此，它们容易受到损伤，并与神经元和肾脏疾病的发生有关。了解这些非再生细胞存活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性节段性肾小球硬化(FSGS)的机制提供线索。我们通过下一代测序探索了同时表现FSGS和Charcot-Marie-Tooth型死亡的患者的疾病基因。结果表明，患者是倒置Form in-2(INF2)错义突变的杂合子。与报道的仅显示FSGS的患者相比，这些突变聚集在更接近N端的位置。利用培养细胞进行的表达研究目前正在进行中，以调查这些突变如何导致足细胞丧失之外的神经元退化。

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.