BỘ KHOA HỌC VÀ CÔNG NGHỆ
HỆ THỐNG THÔNG TIN KHOA HỌC VÀ CÔNG NGHỆ

Lọc theo danh mục
  • Năm xuất bản
    Xem thêm
  • Lĩnh vực
liên kết website
Lượt truy cập
 Lượt truy cập :  22,568,743
  • Công bố khoa học và công nghệ Việt Nam

Nhi khoa

Vũ Thị Thơm(1), Nguyễn Quỳnh Hương, Phạm Văn Đếm, Đinh Đoàn Long(2)

Xét nghiệm gen cho trẻ em mắc hội chứng thận hư tiên phát kháng Corticosteroid: Cần thiết hay không?

The necessity of genetic testing for pediatric steroid- Resistant nephrotic syndrome

TC Khoa học Y dược – Đại học Quốc gia Hà Nội

2018

01

11-19

2615-9309

Hội chứng thận hư tiên phát, Xét nghiệm gen, Liệu pháp miễn dịch, Trẻ em, Corticosteroid

Primary nephrotic syndrome, Gene panel, Immunotherapy, Children, Corticosteroid

Hội chứng thận hư tiên phát (HCTHTP) là một trong những bệnh lý về thận phổ biến nhất ở trẻ em có thể tiến triển thành suy thận hoặc bệnh thận giai đoạn cuối, thậm chí dẫn đến tử vong. Hiện nay, nhiều nghiên cứu chỉ ra có mối liên hệ giữa đa hình di truyền của nhiều gen có liên quan tới HCTHTP. Cùng với tiến bộ của công nghệ giải trình tự gen, các nhà khoa học đưa ra các danh sách gen phù hợp để tư vấn chẩn đoán và điều trị cho từng trường hợp HCTH. Đối với HCTHTP bẩm sinh, các gen NPHS1, NPHS2, WT1, LAMB2, PLCE1, LMX1B được cho là có liên quan chặt chẽ. Đối với HCTHTP trẻ em, các gen NPHS1, NPHS2, WT1, LAMB2, PLCE1, TRPC6, ACTN4, ADCK4, COQ2, COQ6 được khuyến cáo để phân tích. Đối với HCTHTP người lớn, các gen NPHS2, TRPC6, INF2, ACTN4, ADCK4 và WT1 được xác định là có vai trò quan trọng. Các gen này được các nhà nghiên cứu khuyên rằng nên được chỉ định trước khi tiến hành điều trị bằng liệu pháp miễn dịch, trước khi sinh thiết thận và trước khi cấy ghép thận nhằm đạt hiệu quả điều trị cao nhất và hạn chế các tác dụng phụ cho bệnh nhân mắc HCTHTP.

Primary nephrotic syndrome is one of the most common kidney disorders in children that could result in renal failure, even death. Many studies showed the correlation between gene polymorphisms and primary nephrotic syndrome. Currently, with rapid innovation of next generation sequencing, appropriate gene panels were recommended to patients with primary nephrotic syndrome to achieve the intended clinical benefits of treatment. NPHS1, NPHS2, WT1, LAMB2, PLCE1, LMX1B genes were known to be closely associated with congenital nephrotic syndrome, while NPHS1, NPHS2, WT1, LAMB2, PLCE1, TRPC6, ACTN4, ADCK4, COQ2, COQ6 were found related to pediatric primary nephrotic syndrome. For adult primary nephrotic syndrome, NPHS2, TRPC6, INF2, ACTN4, ADCK4 and WT1 were proved important. These diagnostic gene panels should be prescribed for primary nephrotic syndrome patients before immunotherapy treatment, renal biopsy, or kidney transplantation to achieve the highest treatment efficacy and to limit unexpected harmful side effects.

TTKHCNQG, CTv 182

Xem toàn văn
  • [1] Boyer O, Benoit G, Gribouval O, Nevo F, Tete MJ, Dantal J, Gilbert-Dussardier B, Touc-hard G, Karras A, Presne C, Grunfeld JP, Legendre C, Joly D, Rieu P, Mohsin N, Hannedouche T, Moal V, Gubler MC, Broutin I, Mollet G, Antignac C. (2011), Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis,J Am Soc Nephrol. 2011; 22: 239-245.
  • [2] Zenker M, Aigner T, Wendler O, Tralau T, Muntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wuhl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dotsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann LM, Reis A. (2004), Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities,Hum Mol Genet. 2004; 13: 2625-2632
  • [3] Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, Johnson RL, Lee B. (1998), Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in Nail Patella syndrome,Nat Genet. 1998; 19: 47-50
  • [4] Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance Ma, Howell DN, Vance JM, Rosenberg PB. (2005), A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis,Science. 2005; 308: 1801-1804
  • [5] Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K. (1998), Postitionally cloned gene for a novel glomerular protein – nephrin- is mutated in congenital nephrotic syndrome,Mol Cell. 1998; 1: 575-582.
  • [6] Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, Basso G, Quinzii C, Angelini C, Hirano M, Naini AB, Navas P, DiMauro S, Montini G. (2005), Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10 responsive condition,Neurology. 2005; 65: 606-608.
  • [7] Kaplan JM, Kim SH, North KN, Rennke H, Correia La, Tong HQ, Mathis BJ, RodriguezPerez JC, Allen PG, Beggs AH, Pollak MR. (2000), Mutations in ACTN4 encoding alpha actinin-4, cause familial focal segmental glomerulosclerosis,Nat Genet. 2000; 24: 251-256.
  • [8] Lovric S, Ashraf S, Tan W, Hildebrandt F. (2016), Genetic testing in steroid resistant nephrotic syndrome: when and how?,Nephrol Dial Transplant. 2016; 31:1802-1813
  • [9] Preston R, Stuart HM, Lennon R. (2017), Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?,Pediatric Nephrology.2017
  • [10] Benoit G, Machuca E, Antignac C. (2010), Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations,Pediatr Nephrol. 2010; 25:1621-1632.
  • [11] Konigshausen E, Sellin L. (2016), Circulating permeability factors in primary focal segmental glomerulosclerosis: a review of proposed candidates,Biomed Res Int. 2016
  • [12] Weber S, Gribouval O, Esquivel EL, Moriniere V, Tete MJ, Legendre C, Niaudet P, Antignac C. (2004), NPHS2 mutation analysis shows genetic heterogeneity of steroid resistant nephrotic syndrome and low post transplant recurrence,Kidney Int. 2004; 66: 571-579.
  • [13] Santin S, Tazon-Vega B, Silva I, Cobo MA, Gimenez I, Ruiz P, Garcia Maset R, Ballarin J, Torra R, Ars E. (2011), Clinical value of NPHS2 analysis in early and adult onset steroid resistant nephrotic syndrome,Clin J Am Soc Nephrol. 2011; 6: 344-354
  • [14] Bierzynska A, Mc Karthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, Nabhan MM, Kerecuk L, Hegde S, Hughes D, Marks S, Feather S, Jones C, Webb NJ, Ognjanovic M, Christian M, Gilbert RD, Sinha MD, Lord GM, Simpson M, Koziell AB, Welsh GI, Saleem MA. (2017), Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management,Kidney Int. 2017; 91:937-947
  • [15] Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P. (2008), The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporin A,Nat Med. 2008; 14: 931-938
  • [16] ] Ruf RG, Lichtenberg A, Karrle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F. (2004), Patients with mutations in NPHS2 (podocin) do not response to standart steroid treatment of nephrotic syndrome,J Am Soc Nephrol. 2004 15: 722-732.
  • [17] Gellermann J, Stefanidis CJ, Mitsioni A, Querfeld U. (2010), Succesful treatment of steroid resistant nephrotic syndrome associated with WT1 mutations,Pediatr Nephrol. 2010; 25: 1285-1289.
  • [18] Giglio S, Provenzano A, Mazzinghi B, Becherucci F, Giunti L, Sansavini G, Ravaglia F, Roperto RM, Faretti S, Benetti E, Rotondi M, Murer L, Lazzeri E, Lasagni L, Materassi M, Romagnani P. (2015), Heterogenous genetic al-terations in sporadic nephrotic syndrome associate with resistance to immunosuppression,J Am Soc Nephrol. 2015; 26:230-236
  • [19] Nguyen TKL, Pham VD, Nguyen TH, Pham TK, Nguyen TQH, Nguyen HH. (2017), Three novel mutations in NPHS1 gene in Vietnamese patients with congentital nephrotic syndrome. Caser Reports in Genetics. 2017,
  • [20] Jun L. (2012), Genetics of nephrotic syndrome in singapore pediatrics patients, in department of pediatrics,
  • [21] 10. Otukesh H, Fereshtehnejad SM, Bakhshayesh M, Hashemi M, Hoseini R, Chalian M, Salami A, Mehdipor L, Rahiminia A. (2009), NPHS2 Mutations in Children with Steroid-Resistant Nephrotic syndrome,Iranian Journal of Kidney Diseases. 2009; 3(2): 99-102
  • [22] Jain V and Vasudevan P. (2014), Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report f-rom a three-generation family,Clin Kidney J. 2014; 7(3): 303-305
  • [23] Tory K, Menyhard DK, Woerner S, Nevo F, Gribouval O, Kerti A, Straner P, Arrondel C, Huynh Cong E, Tulassay T, Mollet G, Perczel A and Antignac C. (2014), Mutation-dependent recessive inheritance of NPHS2-associated steroid-resistant nephrotic syndrome,Nat Genet. 2014; 46(3): 299-304
  • [24] Berdeli A, Yavascan O, Serdaroqlu E, Bak M, Aksu N, Oner A, Anarat A, Donmez O, Yildiz N, Sever L, Tabel Y, Dusunsel R, Sonmez F, Cakar N. (2007), NPHS2 (podocin) mutations in Turkish children with idiopathic nephritic syndrome,Pediatr Nephrol. 2007; 22(12): 2031-2040
  • [25] Frishberg Y, Megged O, Shapira E, Feinstein S, Raas-Rothschild A. (2002), Mutations in NPHS2 encoding podocin are a prevalent cause of steroid resistant nephritic syndrome among Israeli-Arab children,J Am Soc Nephrol, 2002; 13(2): 400-405
  • [26] Boute N, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C. (2000), NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid resistant nephritic syndrome,Nature genetics. 2000; 24(4): 349-354
  • [27] Hugh MC, Wherlock M, Ognjanovic M, Kerecuk L, Hegde S, Feather S, Krischock L, Jones C, Sinha MD, Webb NJA, Martin C, Marks S, Koziell A, Welsh GI and Saleem MA. (2013), Simultaneous Sequencing of 24 Genes Associated with Steroid-Resistant Nephrotic Syndrome,Clin J Am Soc Nephrol. 2013; 8(4): 637-648
  • [28] Zagury A, Oliveira AL, Montalvao JA, Novaes RH, Sa VM, Moraes CA, and Tavares S. (2013), Steroidresistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease,J Bras Nefrol. 2013; 35(3): 191-199
  • [29] Sang NN. (1999), Evaluation of treatment outcome using methylprednisolon and changing of immunoresponse before and after treatment of primary nephrotic syndrome in pediatrics patients,Department of pediatrics, Hanoi Medical University, Vietnam.
  • [30] Kang HG, Cheong HII. (2015), Nephrotic syndrome: what's new, what's hot,Korean J Pediatr. 2015; 58(8): 275-282.