Journal of Diagnostics Concepts & Practice ›› 2021, Vol. 20 ›› Issue (03): 245-250.doi: 10.16150/j.1671-2870.2021.03.004
• Academic trend at home and abroad • Previous Articles Next Articles
Received:2021-05-17
Online:2021-06-25
Published:2022-06-28
CLC Number:
| 遗传模式 | 突变基因 | 突变类型 | 临床特征 | 进展至ESRD风险 |
|---|---|---|---|---|
| X连锁显性 | COL4A5 | 纯合（男性） | 进展至ESRD的概率以及出现肾外表现的时间受基因型影响 | 100% |
| 杂合（女性） | 影响疾病进展的危险因素包括肉眼血尿、SNHL、蛋白尿、GBM增厚和分层 | 最高可至25% | ||
| 常染色体隐性 | COL4A3或 COL4A4 | 纯合或复合杂合 | 进展至ESRD的概率以及出现肾外表现的时间受基因型影响 | 100% |
| 常染色体显性 | 杂合 | 包括既往被诊断为TBMN/BFH的肾性血尿患者,影响疾病进展的危险因素有蛋白尿、FSGS、GBM增厚和分层、SNHL、患者或家系内成员有疾病进展的证据、合并修饰基因 | 有疾病进展危险因素的患者至少20%,无危险因素的患者<1% | |
| 双基因 | COL4A3、 COL4A4及 COL4A5 | COL4A3和COL4A4 基因反式突变 | 临床表现和遗传模式类似常染色体隐性遗传 | 最高可至100% |
| COL4A3和COL4A4 基因顺式突变 | 临床表现和遗传模式类似常染色体显性遗传 | 最高可至20% | ||
| COL4A5和COL4A3 或COL4A4基因突变 | 不符合孟德尔遗传模式 | 最高可至100% （男性患者） |
| 拟表型基因 | 已报道的修饰基因变异位点 |
|---|---|
| MYH9：Fechtner综合征（OMIM155100） COL4A1, COL4A2：HANAC综合征（OMIM611773） CFHR5：电子致密物沉积病（OMIM 134370）;CFHR5相关肾病（OMIM 614809） FN1：纤维连接蛋白肾小球病（OMIM601894） LMX1B：指甲-髌骨综合征（OMIM 161200） | MYO1E（c.2627C>G; p.Thr876Arg,c.352A>G; p.Lys118Glu） MYH9（c.4952T>C; p.Met1651Thr） LAMA5（c.3728C>T; p.Pro1243Leu） NPHS2（c.686G>A; p.Arg229Gln） |
| [1] | Alport AC. Hereditary familial congenital haemorrhagic nephritis[J]. Br Med J, 1927, 1(3454):504-506. |
| [2] |
Flinter F. Alport's syndrome[J]. J Med Genet, 1997, 34(4):326-330.
pmid: 9138159 |
| [3] |
Gregory MC, Terreros DA, Barker DF, et al. Alport syndrome--clinical phenotypes, incidence, and pathology[J]. Contrib Nephrol, 1996, 117:1-28.
pmid: 8801040 |
| [4] |
Savige J, Gregory M, Gross O, et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy[J]. J Am Soc Nephrol, 2013, 24(3):364-375.
doi: 10.1681/ASN.2012020148 pmid: 23349312 |
| [5] |
ALPORT综合征诊疗共识专家组. Alport综合征诊断和治疗专家推荐意见[J]. 中华肾脏病杂志, 2018, 34(3):227-231.
doi: 10.3760/cma.j.issn.1001-7097.2018.03.014 |
| [6] |
Wang YY, Savige J. The epidemiology of thin basement membrane nephropathy[J]. Semin Nephrol, 2005, 25(3):136-139.
pmid: 15880322 |
| [7] |
Matthaiou A, Poulli T, Deltas C. Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or COL4A4 mutations: a systematic review[J]. Clin Kidney J, 2020, 13(6):1025-1036.
doi: 10.1093/ckj/sfz176 pmid: 33391746 |
| [8] |
Demir E, Caliskan Y. Variations of type Ⅳ collagen-encoding genes in patients with histological diagnosis of focal segmental glomerulosclerosis[J]. Pediatr Nephrol, 2020, 35(6):927-936.
doi: 10.1007/s00467-019-04282-y pmid: 31254113 |
| [9] | Li Y, Groopman EE, D'Agati V, et al. Type Ⅳ collagen mutations in familial IgA nephropathy[J]. Kidney Int Rep, 2020, 5(7):1075-1078. |
| [10] | Barua M, Paterson AD. Population-based studies reveal an additive role of type Ⅳ collagen variants in hematuria and albuminuria[J/OL]. Pediatr Nephrol, 2021-02-26[2021-05-17]. https://pubmed.ncbi.nlm.nih.gov/33635378/. |
| [11] | Furlano M, Martínez V, Pybus M, et al. Clinical and genetic features of autosomal dominant Alport syndrome: a cohort study[J/OL]. Am J Kidney Dis, 2021-04-07[2021-05-17]. https://pubmed.ncbi.nlm.nih.gov/33838161/. |
| [12] |
Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen Ⅳ α345: a position paper of the Alport Syndrome Classification Working Group[J]. Kidney Int, 2018, 93(5):1045-1051.
doi: 10.1016/j.kint.2017.12.018 URL |
| [13] |
Groopman EE, Marasa M, Cameron-Christie S, et al. Diag-nostic utility of exome sequencing for kidney disease[J]. N Engl J Med, 2019, 380(2):142-151.
doi: 10.1056/NEJMoa1806891 URL |
| [14] | Quinlan C, Rheault MN. Genetic basis of type Ⅳ collagen disorders of the kidney[J/OL]. Clin J Am Soc Nephrol. 2021-04-13[2021-05-17]. https://pubmed.ncbi.nlm.nih.gov/33849932/. |
| [15] |
Gross O, Licht C, Anders HJ, et al. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy[J]. Kidney Int, 2012, 81(5):494-501.
doi: 10.1038/ki.2011.407 URL |
| [16] | Zhang Y, Böckhaus J, Wang F, et al. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome[J/OL]. Pediatr Nephrol. 2021-03-27[2021-05-17]. https://pubmed.ncbi.nlm.nih.gov/33772369/. |
| [17] |
Gross O, Tönshoff B, Weber LT, et al. A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport′s syndrome[J]. Kidney Int, 2020, 97(6):1275-1286.
doi: 10.1016/j.kint.2019.12.015 URL |
| [18] |
Stock J, Kuenanz J, Glonke N, et al. Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations[J]. Pediatr Nephrol, 2017, 32(1):131-137.
doi: 10.1007/s00467-016-3452-z URL |
| [19] |
Temme J, Peters F, Lange K, et al. Incidence of renal failure and nephroprotection by RAAS inhibition in hete-rozygous carriers of X-chromosomal and autosomal recessive Alport mutations[J]. Kidney Int, 2012, 81(8):779-783.
doi: 10.1038/ki.2011.452 URL |
| [20] |
Kashtan CE. Alport syndrome: achieving early diagnosis and treatment[J]. Am J Kidney Dis, 2021, 77(2):272-279.
doi: 10.1053/j.ajkd.2020.03.026 URL |
| [21] |
Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020[J]. Pediatr Nephrol, 2021, 36(3):711-719.
doi: 10.1007/s00467-020-04819-6 URL |
| [22] |
Savige J. Should we diagnose autosomal dominant alport syndrome when there is a pathogenic heterozygous COL4A3 or COL4A4 variant?[J]. Kidney Int Rep, 2018, 3(6):1239-1241.
doi: 10.1016/j.ekir.2018.08.002 pmid: 30450445 |
| [23] | Chan MM, Gale DP. Isolated microscopic haematuria of glomerular origin: clinical significance and diagnosis in the 21st century[J]. Clin Med (Lond), 2015, 15(6):576-580. |
| [24] | Uliana V, Sebastio P, Riva M, et al. Deciphering the pathogenesis of the COL4-related hematuric nephritis: A genotype/phenotype study[J]. Mol Genet Genomic Med, 2021, 9(2):e1576. |
| [25] |
Moreno JA, Yuste C, Gutiérrez E, et al. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: a review[J]. Pediatr Nephrol, 2016, 31(4):523-533.
doi: 10.1007/s00467-015-3119-1 URL |
| [26] |
Murray SL, Dorman A, Benson KA, et al. Utility of genomic testing after renal biopsy[J]. Am J Nephrol, 2020, 51(1):43-53.
doi: 10.1159/000504869 pmid: 31822006 |
| [27] | Jayasinghe K, Stark Z, Kerr PG, et al. Clinical impact of genomic testing in patients with suspected monogenic kidney disease[J]. Genet Med, 2021, 23(1):183-191. |
| [28] |
Vos P, Zietse R, van Geel M, et al. Diagnosing Alport syndrome: lessons from the pediatric ward[J]. Nephron, 2018, 140(3):203-210.
doi: 10.1159/000492438 URL |
| [29] |
Deltas C, Pierides A, Voskarides K. Molecular genetics of familial hematuric diseases[J]. Nephrol Dial Transplant, 2013, 28(12):2946-2960.
doi: 10.1093/ndt/gft253 URL |
| [30] |
Savige J, Ariani F, Mari F, et al. Expert consensus guidelines for the genetic diagnosis of Alport syndrome[J]. Pediatr Nephrol, 2019, 34(7):1175-1189.
doi: 10.1007/s00467-018-3985-4 pmid: 29987460 |
| [31] | Savige J, Storey H, Watson E, et al. Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria[J/OL]. Eur J Hum Genet, 2021-04-15[2021-05-17]. https://pubmed.ncbi.nlm.nih.gov/33854215/. |
| [32] | Yamamura T, Nozu K, Minamikawa S, et al. Comparison between conventional and comprehensive sequencing approaches for genetic diagnosis of Alport syndrome[J]. Mol Genet Genomic Med, 2019, 7(9):e883. |
| [33] |
Moreno JA, Sevillano á, Gutiérrez E, et al. Glomerular hematuria: cause or consequence of renal inflammation?[J]. Int J Mol Sci, 2019, 20(9):2205.
doi: 10.3390/ijms20092205 URL |
| [34] |
Bish DR, Bish EK, El-Hajj H, et al. A robust pooled testing approach to expand COVID-19 screening capacity[J]. PLoS One, 2021, 16(2):e0246285.
doi: 10.1371/journal.pone.0246285 URL |
| [35] |
Lin F, Bian F, Zou J, et al. Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease[J]. BMC Nephrol, 2014, 15:175.
doi: 10.1186/1471-2369-15-175 URL |
| [36] |
Zhang Y, Ding J, Wang S, et al. Reassessing the pathogenicity of c.2858G>T(p.(G953V)) in COL4A5 Gene: report of 19 Chinese families[J]. Eur J Hum Genet, 2020, 28(2):244-252.
doi: 10.1038/s41431-019-0523-1 URL |
| [37] |
Shulman C, Liang E, Kamura M, et al. Type Ⅳ collagen variants in CKD: performance of computational predictions for identifying pathogenic variants[J]. Kidney Med, 2021, 3(2):257-266.
doi: 10.1016/j.xkme.2020.12.007 URL |
| [38] |
Omachi K, Kamura M, Teramoto K, et al. A split-luciferase-based trimer formation assay as a high-throughput screening platform for therapeutics in alport syndrome[J]. Cell Chem Biol, 2018, 25(5):634-643.
doi: S2451-9456(18)30043-6 pmid: 29526710 |
| [39] |
Fallerini C, Baldassarri M, Trevisson E, et al. Alport syndrome: impact of digenic inheritance in patients management[J]. Clin Genet, 2017, 92(1):34-44.
doi: 10.1111/cge.12919 pmid: 27859054 |
| [40] |
Horinouchi T, Nozu K, Yamamura T, et al. Detection of splicing abnormalities and genotype-phenotype correlation in X-linked Alport syndrome[J]. J Am Soc Nephrol, 2018, 29(8):2244-2254.
doi: 10.1681/ASN.2018030228 pmid: 29959198 |
| [41] |
Boeckhaus J, Hoefele J, Riedhammer KM, et al. Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial[J]. Clin Genet, 2021, 99(1):143-156.
doi: 10.1111/cge.13861 pmid: 33040356 |
| [42] |
Horinouchi T, Yamamura T, Nagano C, et al. Heterozygous urinary abnormality-causing variants of COL4A3 and COL4A4 affect severity of autosomal recessive Alport syndrome[J]. Kidney 360, 2020, 1:936-942.
doi: 10.34067/KID.0000372019 pmid: 35369551 |
| [43] | Yamamura T, Nozu K, Fu XJ, et al. Natural history and genotype-phenotype correlation in female X-linked Alport syndrome[J]. Kidney Int Rep, 2017, 2(5):850-855. |
| [1] | HAO Xu, WANG Weiming. Fabry disease presenting with renal disease as the main manifestation diagnosed by renal biopsy: a case report [J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 527-529. |
| [2] | SHI Xia, MA Xin, WANG Zhenyan, ZHANG Hui, LIU Shaojun. Analysis on the clinicopathological characteristics and follow-up of 32 patients with human immunodeficiency virus infection and chronic kidney diseases [J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 437-443. |
| [3] | HUANG Juan, ZHU Xiaolei, LI Xiao, CHEN Kemin, YAN Fuhua, XU Xueqin. Study on blood oxygen level-dependent magnetic resonance imaging for the assessment of early renal hypoxia in chronic kidney disease [J]. Journal of Diagnostics Concepts & Practice, 2022, 21(03): 385-389. |
| [4] | . [J]. Journal of Diagnostics Concepts & Practice, 2021, 20(02): 125-129. |
| [5] | . [J]. Journal of Diagnostics Concepts & Practice, 2021, 20(02): 213-215. |
| [6] | . [J]. Journal of Diagnostics Concepts & Practice, 2020, 19(06): 613-617. |
| [7] | . [J]. Journal of Diagnostics Concepts & Practice, 2020, 19(03): 229-231. |
| [8] | . [J]. Journal of Diagnostics Concepts & Practice, 2019, 18(06): 698-703. |
| [9] | WANG Yuanyuan, FAN Qiuling. Clinical value of serum procalcitonin in patients of chronic kidney disease with bacterial infection [J]. Journal of Diagnostics Concepts & Practice, 2019, 18(03): 353-359. |
| [10] | WU Lin, ZHENG Ge, TAO Ting. Angiotensin-converting enzyme gene insertion/deletion polymorphism and decline of renal function in elderly [J]. Journal of Diagnostics Concepts & Practice, 2019, 18(2): 204-208. |
| [11] | JIAO Jieru, LI Yanran, CHEN Xiaonong, LIN Qing. Change and significance of clinical indices on treatment with tacrolimus combined with piperazine ferulate for primary nephrotic syndrome in elderly [J]. Journal of Diagnostics Concepts & Practice, 2019, 18(1): 104-106. |
| [12] | WANG Yimei, TENG Jie, SHEN Bo, XU Jiarui, JIANG Wuhua, YU Jiawei, HU Jiachang, DING Xiaoqiang. Real-time electronic alert system improving the detection of acute kidney injury [J]. Journal of Diagnostics Concepts & Practice, 2017, 16(06): 596-600. |
| [13] | XING Peng, LIU Simeng, CHEN Zijin, REN Hong, CHEN Xiaonong, LI Xiao. Outcome and risk factors of patients with renal failure due to ANCA-associated vasculitis after emergency hemodialysis [J]. Journal of Diagnostics Concepts & Practice, 2017, 16(04): 384-389. |
| [14] | . [J]. Journal of Diagnostics Concepts & Practice, 2017, 16(04): 347-352. |
| [15] | LI Huilin, WU Ping, LIU Shuang, JIANG Gengru. Soluble Klotho attenuates high glucose-induced renal fibrosis through inhibiting STAT3 pathway [J]. Journal of Diagnostics Concepts & Practice, 2017, 16(04): 371-376. |
| Viewed | ||||||
|
Full text |
|
|||||
|
Abstract |
|
|||||
