Feng Zhao1, Zihua Yu2, Yonghui Yang1, Xiaojing Nie1, Jun Huang1, Chengfeng Wang1, Guizhi Xia1, Guangming Chen1. 1. Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command, the People's Liberation Army (PLA), Fuzhou 350025, China. 2. Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command, the People's Liberation Army (PLA), Fuzhou 350025, China. Email: zihuayu@vip.sina.com.
Abstract
OBJECTIVE: Previous studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established. METHOD: Peripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion. RESULT: Fifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11T>C, IVS2-86T>A, 279T>C (D93D), IVS6-181G>A, 718C>T (L240F), 1678A>G (T560A), IVS16-35A>G, IVS18+48T>A, IVS19+38G>A and IVS25+13C>T were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states. CONCLUSION: MYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.
OBJECTIVE: Previous studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established. METHOD: Peripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion. RESULT: Fifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11T>C, IVS2-86T>A, 279T>C (D93D), IVS6-181G>A, 718C>T (L240F), 1678A>G (T560A), IVS16-35A>G, IVS18+48T>A, IVS19+38G>A and IVS25+13C>T were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states. CONCLUSION:MYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.