Abstract Objective Steroid-resistant nephrotic syndrome (SRNS) with MYO1E mutations has been identified as autosomal recessive focal segmental glomerulosclerosis (FSGS). To date, only two homozygous mutations in the MYO1E gene were reported in three families with FSGS. This study aimed to examine mutations in the MYO1E gene in children with familial SRNS in the Han Chinese ethnic group. Methods Between 2005 and 2010, peripheral blood samples were collected from the probands, their siblings and parents of four families with autosomal recessive SRNS in the Han Chinese ethnic group. Four probands were studied from nine patients. The mutational analysis of MYO1E was performed by polymerase chain reaction and direct DNA sequencing. Fifty-nine healthy volunteers with normal urine analysis were included as controls. Results Twenty-five MYO1E variants in the prohands from 4 families with SRNS were identified in this study. Among them, 24 variants were found in NCBI dbSNP. One heterozygous mutation IVS21-85G>A was found in the prohand from Family D, whereas it was absent in 59 normal Chinese controls. No splice site change caused by IVS21-85G>A was reported by analysis with NetGene2. Conclusions MYO1E mutations are not a major cause of Chinese familial SRNS in this study.
ZHAO Feng,YU Zi-Hua,YANG Yong-Hui et al. Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome[J]. CJCP, 2014, 16(4): 349-355.
ZHAO Feng,YU Zi-Hua,YANG Yong-Hui et al. Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome[J]. CJCP, 2014, 16(4): 349-355.
Benoit G, Machuca E, Antignac C. Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations[J]. Pediatr Nephrol, 2010, 25(9): 1621-1632.
[2]
Lowik MM, Groenen PJ, Levtchenko EN, et al. Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis-a review[J]. Eur J Pediatr, 2009, 168(11): 1291-1304.
[3]
Gbadegesin R, Lavin P, Foreman J, et al. Pathogenesis and therapy of focal segmental glomerulosclerosis: an update[J]. Pediatr Nephrol, 2011, 26(7): 1001-1015.
[4]
Mele C, Iatropoulos P, Donadelli R, et al. MYO1E mutations and childhood familial focal segmental glomerulosclerosis[J]. N Engl J Med, 2011, 365(4): 295-306.
[5]
Sanna-Cherchi S, Burgess KE, Nees SN, et al. Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephritic syndrome[J]. Kidney Int, 2011, 80(4): 389-396.
[6]
Pollak MR. Inherited podocytopathies: FSGS and nephrotic syndrome from a genetic viewpoint[J]. J Am Soc Nephrol, 2002, 13(12): 3016-3023.
[7]
Niaudet P. Podocin and nephrotic syndrome: implications for the clinician[J]. J Am Soc Nephrol, 2004, 15(3): 832-834.
[8]
Dai J, Sheetz MP. Regulation of endocytosis, exocytosis, and shape by membrane tension[J]. Cold Spring Harb Symp Quant Biol, 1995, 60: 567-571.
[9]
McConnell RE, Tyska MJ. Leveraging the membrane-cytoskeleton interface with myosin-1[J]. Trends Cell Biol, 2010, 20(7): 418-426.
[10]
Soda K, Balkin DM, Ferguson SM, et al. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes[J]. J Clin Invest, 2012, 122(12): 4401-4411.
[11]
Bi J, Chase SE, Pellenz CD, et al. Myosin 1e is a component of the glomerular slit diaphragm complex that regulates actin reorganization during cell-cell contact formation in podocytes[J]. Am J Physiol Renal Physiol, 2013, 305(4): F532-F544.
[12]
Krendel M, Kim SV, Willinger T, et al. Disruption of Myosin 1e promotes podocyte injury[J]. J Am Soc Nephrol, 2009, 20(1):86-94.
[13]
Chase SE, Encina CV, Stolzenburg LR, et al. Podocyte-specific knockout of myosin 1e disrupts glomerular filtration[J]. Am J Physiol Renal Physiol, 2012, 303(7): F1099-F1106.
McCarthy HJ, Bierzynska A, Wherlock M, et al. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome[J]. Clin J Am Soc Nephrol, 2013, 8(4): 637-648.
