Systematic Review of Clinical Characteristics and Genotype-Phenotype Correlation in LAMB2-Associated Disease

1. Zenker M, Aigner T, Wendler O, et al. Human laminin beta2

deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet.

2004;13:2625–2632. https://doi.org/10.1093/hmg/ddh284

2. Bredrup C, Matejas V, Barrow M, et al. Ophthalmological

aspects of Pierson syndrome. Am J Ophthalmol. 2008;146:

602–611. https://doi.org/10.1016/j.ajo.2008.05.039

3. Wuhl E, Kogan J, Zurowska A, et al. Neurodevelopmental

deficits in Pierson (microcoria-congenital nephrosis) syndrome. Am J Med Genet A. 2007;143:311–319. https://doi.org/

10.1002/ajmg.a.31564

4. Aumailley M. The laminin family. Cell Adh Migr. 2013;7:48–

55. https://doi.org/10.4161/cam.22826

5. Kikkawa Y, Hashimoto T, Takizawa K, et al. Laminin beta2

variants associated with isolated nephropathy that impact

matrix regulation. JCI Insight. 2021;6:e145908. https://doi.org/

10.1172/jci.insight.145908

6. Nagano C, Yamamura T, Horinouchi T, et al. Comprehensive

genetic diagnosis of Japanese patients with severe proteinuria. Sci Rep. 2020;10:270. https://doi.org/10.1038/s41598-01957149-5

7. Abid A, Shahid S, Shakoor M, Lanewala AA, Hashmi S,

Khaliq S. Screening of the LAMB2, WT1, NPHS1, and NPHS2

Genes in Pediatric Nephrotic Syndrome. Front Genet. 2018;9:

214. https://doi.org/10.3389/fgene.2018.00214

8. Joshi A, Sinha A, Sharma A, et al. Next-generation

sequencing for congenital nephrotic syndrome: a multicenter cross-sectional study from India. Indian Pediatr.

2021;58:445–451. https://doi.org/10.1007/s13312-021-2215-5

9. Matejas V, Hinkes B, Alkandari F, et al. Mutations in the human laminin beta2 (LAMB2) gene and the associated

phenotypic spectrum. Hum Mutat. 2010;31:992–1002. https://

doi.org/10.1002/humu.21304

10. Minamikawa S, Miwa S, Inagaki T, et al. Molecular mechanisms determining severity in patients with Pierson syndrome. J Hum Genet. 2020;65:355–362. https://doi.org/10.

1038/s10038-019-0715-0

11. Hasselbacher K, Wiggins RC, Matejas V, et al. Recessive

missense mutations in LAMB2 expand the clinical spectrum

of LAMB2-associated disorders. Kidney Int. 2006;70:1008–

1012. https://doi.org/10.1038/sj.ki.5001679

12. Matejas V, Al-Gazali L, Amirlak I, Zenker M. A syndrome

comprising childhood-onset glomerular kidney disease and

ocular abnormalities with progressive loss of vision is caused

by mutated LAMB2. Nephrol Dial Transplant. 2006;21:3283–

3286. https://doi.org/10.1093/ndt/gfl463

13. Zurowska A, Zaluska-Lesniewska I, Zenker M. LAMB2 gene

mutation as a cause of congenital nephrotic syndrome with

distinct eye abnormalities and hypotonia. Article in Polish.

Przegl Lek. 2006;63(suppl 3):37–39.

14. Choi HJ, Lee BH, Kang JH, et al. Variable phenotype of Pierson syndrome. Pediatr Nephrol. 2008;23:995–1000. https://

doi.org/10.1007/s00467-008-0748-7

1820

R Suzuki et al.: Genotype-Phenotype Correlation in LAMB2 Disease

15. Maselli RA, Ng JJ, Anderson JA, et al. Mutations in LAMB2

causing a severe form of synaptic congenital myasthenic

syndrome. J Med Genet. 2009;46:203–208. https://doi.org/10.

1136/jmg.2008.063693

16. Machuca E, Benoit G, Nevo F, et al. Genotype-phenotype

correlations in non-Finnish congenital nephrotic syndrome.

J Am Soc Nephrol. 2010;21:1209–1217. https://doi.org/10.

1681/ASN.2009121309

17. Zhao D, Ding J, Wang F, et al. The first Chinese Pierson

syndrome with novel mutations in LAMB2. Nephrol Dial

Transplant. 2010;25:776–778. https://doi.org/10.1093/ndt/

gfp563

18. Mohney BG, Pulido JS, Lindor NM, et al. A novel mutation of

LAMB2 in a multigenerational Mennonite family reveals a

new phenotypic variant of pierson syndrome. Ophthalmology. 2011;118:1137–1144. https://doi.org/10.1016/j.ophtha.2010.10.009

19. Aydin B, Ipek MS, Ozaltin F, et al. A novel mutation of laminin

beta-2 gene in Pierson syndrome manifested with nephrotic

syndrome in the early neonatal period. Genet Couns. 2013;24:

141–147.

20. Togawa H, Nakanishi K, Mukaiyama H, et al. First Japanese

case of Pierson syndrome with mutations in LAMB2. Pediatr

Int. 2013;55:229–231. https://doi.org/10.1111/j.1442-200X.2012.

03629.x

21. Lovric S, Fang H, Vega-Warner V, et al. Rapid detection of

monogenic causes of childhood-onset steroid-resistant

nephrotic syndrome. Clin J Am Soc Nephrol. 2014;9:1109–

1116. https://doi.org/10.2215/CJN.09010813

22. Cil O, Besbas N, Duzova A, et al. Genetic abnormalities and

prognosis in patients with congenital and infantile nephrotic

syndrome. Pediatr Nephrol. 2015;30:1279–1287. https://doi.

org/10.1007/s00467-015-3058-x

23. Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in

29.5% of cases of steroid-resistant nephrotic syndrome. J Am

Soc Nephrol. 2015;26:1279–1289. https://doi.org/10.1681/

ASN.2014050489

24. Willig LK, Petrikin JE, Smith LD, et al. Whole-genome

sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and

clinical findings. Lancet Respir Med. 2015;3:377–387. https://

doi.org/10.1016/S2213-2600(15)00139-3

25. Zemrani B, Cachat F, Bonny O, et al. A novel LAMB2 gene

mutation associated with a severe phenotype in a neonate

with Pierson syndrome. Eur J Med Res. 2016;21:19. https://

doi.org/10.1186/s40001-016-0215-z

26. Peña-González L, Guerra-García P, Sánchez-Calvín MT, Delgado-Ledesma F, de Alba-Romero C. New genetic mutation

associated with Pierson syndrome. An Pediatr (Barc).

2016;85:321–322. https://doi.org/10.1016/j.anpedi.2016.01.025

27. Qiu L, Zhou J. Simultaneous mutations of LAMB2 and

NPHP1genes in a Chinese girl with isolated congenital

nephrotic syndrome: a case report. BMC Pediatr. 2016;16:44.

https://doi.org/10.1186/s12887-016-0583-0

28. Falix FA, Bennebroek CA, van der Zwaag B, Lapid-Gortzak R,

Florquin S, Oosterveld MJ. A novel mutation of laminin beta2

(LAMB2) in two siblings with renal failure. Eur J Pediatr.

2017;176:515–519. https://doi.org/10.1007/s00431-017-2871-6

29. Kino J, Tsukaguchi H, Kimata T, et al. Nephron development and extrarenal features in a child with congenital

Kidney International Reports (2023) 8, 1811–1821

R Suzuki et al.: Genotype-Phenotype Correlation in LAMB2 Disease

nephrotic syndrome caused by null LAMB2 mutations.

BMC Nephrol. 2017;18:220. https://doi.org/10.1186/s12882017-0632-4

30. Sen ES, Dean P, Yarram-Smith L, et al. Clinical genetic testing

using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations. J Med

Genet. 2017;54:795–804. https://doi.org/10.1136/jmedgenet2017-104811

31. Wang F, Zhang Y, Mao J, et al. Spectrum of mutations in

Chinese children with steroid-resistant nephrotic syndrome.

Pediatr Nephrol. 2017;32:1181–1192. https://doi.org/10.1007/

s00467-017-3590-y

32. Warejko JK, Tan W, Daga A, et al. Whole exome sequencing

of patients with steroid-resistant nephrotic syndrome. Clin J

Am Soc Nephrol. 2018;13:53–62. https://doi.org/10.2215/CJN.

04120417

33. Arima M, Tsukamoto S, Akiyama R, et al. Ocular findings in a

case of Pierson syndrome with a novel mutation in laminin

ß2 gene. J Am Assoc Pediatr Ophthalmol Strabismus.

2018;22:401–403.e401.

34. Schapiro D, Daga A, Lawson JA, et al. Panel sequencing

distinguishes monogenic forms of nephritis from nephrosis

in children. Nephrol Dial Transplant. 2019;34:474–485. https://

doi.org/10.1093/ndt/gfy050

35. Wojcik MH, Schwartz TS, Thiele KE, et al. Infant mortality: the

contribution of genetic disorders. J Perinatol. 2019;39:1611–

1619. https://doi.org/10.1038/s41372-019-0451-5

36. Kulali F, Calkavur S, Basaran C, Serdaroglu E, Kose M, Saka

Guvenc M. A new mutation associated with Pierson syndrome. Arch Argent Pediatr. 2020;118:e288–e291. https://doi.

org/10.5546/aap.2020.eng.e288

37. Park E, Lee C, Kim NKD, et al. Genetic study in Korean

pediatric patients with steroid-resistant nephrotic syndrome or focal segmental glomerulosclerosis. J Clin

Med. 2020;9:2013. https://doi.org/10.3390/jcm9062013

38. Sakuraya K, Nozu K, Murakami H, et al. An extremely mild

clinical course in a case with LAMB2-associated nephritis

diagnosed with next-generation sequencing. CEN Case

Kidney International Reports (2023) 8, 1811–1821

CLINICAL RESEARCH

Rep. 2021;10:359–363. https://doi.org/10.1007/s13730-02100574-1

39. Zenker M, Pierson M, Jonveaux P, Reis A. Demonstration of

two novelLAMB2 mutations in the original Pierson syndrome

family reported 42 years ago. Am J Med Genet A. 2005;138A:

73–74. https://doi.org/10.1002/ajmg.a.30894

40. Mbarek IB, Abroug S, Omezzine A, et al. Novel mutations in

steroid-resistant nephrotic syndrome diagnosed in Tunisian

children. Pediatr Nephrol. 2010;26:241–249. https://doi.org/10.

1007/s00467-010-1694-8

41. Kagan M, Cohen AH, Matejas V, Vlangos C, Zenker M.

A milder variant of Pierson syndrome. Pediatr Nephrol.

2008;23:323–327. https://doi.org/10.1007/s00467-007-0624-x

42. Richards S, Aziz N, Bale S, et al. Standards and guidelines for

the interpretation of sequence variants: a joint consensus

recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–424. https://doi.org/10.1038/

gim.2015.30

43. Kanda Y. Investigation of the freely available easy-to-use

software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–458. https://doi.org/10.1038/bmt.2012.244

44. Funk SD, Lin MH, Miner JH. Alport syndrome and Pierson

syndrome: diseases of the glomerular basement membrane.

Matrix Biol. 2018;71-72:250–261. https://doi.org/10.1016/j.

matbio.2018.04.008

45. Boyer O, Schaefer F, Haffner D, et al. Management of

congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group. Nat Rev Nephrol.

2021;17:277–289. https://doi.org/10.1038/s41581-020-00384-1

46. Nozu K, Nakanishi K, Abe Y, et al. A review of clinical

characteristics and genetic backgrounds in Alport syndrome. Clin Exp Nephrol. 2019;23:158–168. https://doi.org/

10.1007/s10157-018-1629-4

47. Guler S, Cimen S, Acott P, Whelan K, Molinari M. Kidney

transplantation in a child with Pierson syndrome. Pediatr

Transplant. 2017;21:10.1111/petr.13076. https://doi.org/10.1111/

petr.13076

1821

...