Identification of a Locus on the X Chromosome Linked to Familial Membranous NephropathyCitation formats

  • External authors:
  • Mallory L Downie
  • Sanjana Gupta
  • Mehmet C Tekman
  • Chris Cheshire
  • Steven Arora
  • Christoph Licht
  • Lisa A Robinson
  • Marina Munoz
  • Alvaro Madrid Aris
  • Ibrahim Al Attrach
  • Daniel P Gale
  • Horia Stanescu
  • Detlef Bockenhauer
  • Robert Kleta

Standard

Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy. / Downie, Mallory L; Gupta, Sanjana; Tekman, Mehmet C; Cheshire, Chris; Arora, Steven; Licht, Christoph; Robinson, Lisa A; Munoz, Marina; Aris, Alvaro Madrid; Al Attrach, Ibrahim; Brenchley, Paul E; Gale, Daniel P; Stanescu, Horia; Bockenhauer, Detlef; Kleta, Robert.

In: Kidney International Reports, Vol. 6, No. 6, 06.2021, p. 1669-1676.

Research output: Contribution to journalArticlepeer-review

Harvard

Downie, ML, Gupta, S, Tekman, MC, Cheshire, C, Arora, S, Licht, C, Robinson, LA, Munoz, M, Aris, AM, Al Attrach, I, Brenchley, PE, Gale, DP, Stanescu, H, Bockenhauer, D & Kleta, R 2021, 'Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy', Kidney International Reports, vol. 6, no. 6, pp. 1669-1676. https://doi.org/10.1016/j.ekir.2021.02.025, https://doi.org/10.1016/j.ekir.2021.02.025

APA

Downie, M. L., Gupta, S., Tekman, M. C., Cheshire, C., Arora, S., Licht, C., Robinson, L. A., Munoz, M., Aris, A. M., Al Attrach, I., Brenchley, P. E., Gale, D. P., Stanescu, H., Bockenhauer, D., & Kleta, R. (2021). Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy. Kidney International Reports, 6(6), 1669-1676. https://doi.org/10.1016/j.ekir.2021.02.025, https://doi.org/10.1016/j.ekir.2021.02.025

Vancouver

Downie ML, Gupta S, Tekman MC, Cheshire C, Arora S, Licht C et al. Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy. Kidney International Reports. 2021 Jun;6(6):1669-1676. https://doi.org/10.1016/j.ekir.2021.02.025, https://doi.org/10.1016/j.ekir.2021.02.025

Author

Downie, Mallory L ; Gupta, Sanjana ; Tekman, Mehmet C ; Cheshire, Chris ; Arora, Steven ; Licht, Christoph ; Robinson, Lisa A ; Munoz, Marina ; Aris, Alvaro Madrid ; Al Attrach, Ibrahim ; Brenchley, Paul E ; Gale, Daniel P ; Stanescu, Horia ; Bockenhauer, Detlef ; Kleta, Robert. / Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy. In: Kidney International Reports. 2021 ; Vol. 6, No. 6. pp. 1669-1676.

Bibtex

@article{983107ad7d8a4c0b8af78edee215deca,
title = "Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy",
abstract = "Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults and is a leading cause of end-stage renal disease due to glomerulonephritis. Primary MN has a strong male predominance, accounting for approximately 65% of cases; yet, currently associated genetic loci are all located on autosomes. Previous reports of familial MN have suggested the existence of a potential X-linked susceptibility locus. Identification of such risk locus may provide clues to the etiology of MN.Methods: We identified 3 families with 8 members affected by primary MN. Genotyping was performed using single-nucleotide polymorphism microarrays, and serum was sent for anti-phospholipase A2 receptor (PLA2R) antibody testing. All affected members were male and connected through the maternal line, consistent with X-linked inheritance. Genome-wide multipoint parametric linkage analysis using a model of X-linked recessive inheritance was conducted, and genetic risk scores (GRSs) based on known MN-associated variants were determined.Results: Anti-PLA2R testing was negative in all affected family members. Linkage analysis revealed a significant logarithm of the odds score (3.260) on the short arm of the X chromosome at a locus of approximately 11 megabases (Mb). Haplotype reconstruction further uncovered a shared haplotype spanning 2 Mb present in all affected individuals from the 3 families. GRSs in familial MN were significantly lower than in anti-PLA2R-associated MN and were not different from controls.Conclusions: Our study identifies linkage of familial membranous nephropathy to chromosome Xp11.3-11.22. Family members affected with MN have a significantly lower GRS than individuals with anti-PLA2R-associated MN, suggesting that X-linked familial MN represents a separate etiologic entity.",
keywords = "LOD score, X-linked, genetic risk score, glomerulonephritis, linkage analysis, membranous nephropathy",
author = "Downie, {Mallory L} and Sanjana Gupta and Tekman, {Mehmet C} and Chris Cheshire and Steven Arora and Christoph Licht and Robinson, {Lisa A} and Marina Munoz and Aris, {Alvaro Madrid} and {Al Attrach}, Ibrahim and Brenchley, {Paul E} and Gale, {Daniel P} and Horia Stanescu and Detlef Bockenhauer and Robert Kleta",
note = "Funding Information: RK, DB, and MLD were supported by St. Peter{\textquoteright}s Trust for Kidney, Bladder, & Prostate Research. MLD was supported by the Kidney Research Scientist Core Education and National Training Program (KRESCENT) Post-Doctoral Fellowship from the Kidney Foundation of Canada . Publisher Copyright: {\textcopyright} 2021 International Society of Nephrology",
year = "2021",
month = jun,
doi = "10.1016/j.ekir.2021.02.025",
language = "English",
volume = "6",
pages = "1669--1676",
journal = "Kidney International Reports",
issn = "2468-0249",
publisher = "Elsevier BV",
number = "6",

}

RIS

TY - JOUR

T1 - Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy

AU - Downie, Mallory L

AU - Gupta, Sanjana

AU - Tekman, Mehmet C

AU - Cheshire, Chris

AU - Arora, Steven

AU - Licht, Christoph

AU - Robinson, Lisa A

AU - Munoz, Marina

AU - Aris, Alvaro Madrid

AU - Al Attrach, Ibrahim

AU - Brenchley, Paul E

AU - Gale, Daniel P

AU - Stanescu, Horia

AU - Bockenhauer, Detlef

AU - Kleta, Robert

N1 - Funding Information: RK, DB, and MLD were supported by St. Peter’s Trust for Kidney, Bladder, & Prostate Research. MLD was supported by the Kidney Research Scientist Core Education and National Training Program (KRESCENT) Post-Doctoral Fellowship from the Kidney Foundation of Canada . Publisher Copyright: © 2021 International Society of Nephrology

PY - 2021/6

Y1 - 2021/6

N2 - Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults and is a leading cause of end-stage renal disease due to glomerulonephritis. Primary MN has a strong male predominance, accounting for approximately 65% of cases; yet, currently associated genetic loci are all located on autosomes. Previous reports of familial MN have suggested the existence of a potential X-linked susceptibility locus. Identification of such risk locus may provide clues to the etiology of MN.Methods: We identified 3 families with 8 members affected by primary MN. Genotyping was performed using single-nucleotide polymorphism microarrays, and serum was sent for anti-phospholipase A2 receptor (PLA2R) antibody testing. All affected members were male and connected through the maternal line, consistent with X-linked inheritance. Genome-wide multipoint parametric linkage analysis using a model of X-linked recessive inheritance was conducted, and genetic risk scores (GRSs) based on known MN-associated variants were determined.Results: Anti-PLA2R testing was negative in all affected family members. Linkage analysis revealed a significant logarithm of the odds score (3.260) on the short arm of the X chromosome at a locus of approximately 11 megabases (Mb). Haplotype reconstruction further uncovered a shared haplotype spanning 2 Mb present in all affected individuals from the 3 families. GRSs in familial MN were significantly lower than in anti-PLA2R-associated MN and were not different from controls.Conclusions: Our study identifies linkage of familial membranous nephropathy to chromosome Xp11.3-11.22. Family members affected with MN have a significantly lower GRS than individuals with anti-PLA2R-associated MN, suggesting that X-linked familial MN represents a separate etiologic entity.

AB - Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults and is a leading cause of end-stage renal disease due to glomerulonephritis. Primary MN has a strong male predominance, accounting for approximately 65% of cases; yet, currently associated genetic loci are all located on autosomes. Previous reports of familial MN have suggested the existence of a potential X-linked susceptibility locus. Identification of such risk locus may provide clues to the etiology of MN.Methods: We identified 3 families with 8 members affected by primary MN. Genotyping was performed using single-nucleotide polymorphism microarrays, and serum was sent for anti-phospholipase A2 receptor (PLA2R) antibody testing. All affected members were male and connected through the maternal line, consistent with X-linked inheritance. Genome-wide multipoint parametric linkage analysis using a model of X-linked recessive inheritance was conducted, and genetic risk scores (GRSs) based on known MN-associated variants were determined.Results: Anti-PLA2R testing was negative in all affected family members. Linkage analysis revealed a significant logarithm of the odds score (3.260) on the short arm of the X chromosome at a locus of approximately 11 megabases (Mb). Haplotype reconstruction further uncovered a shared haplotype spanning 2 Mb present in all affected individuals from the 3 families. GRSs in familial MN were significantly lower than in anti-PLA2R-associated MN and were not different from controls.Conclusions: Our study identifies linkage of familial membranous nephropathy to chromosome Xp11.3-11.22. Family members affected with MN have a significantly lower GRS than individuals with anti-PLA2R-associated MN, suggesting that X-linked familial MN represents a separate etiologic entity.

KW - LOD score

KW - X-linked

KW - genetic risk score

KW - glomerulonephritis

KW - linkage analysis

KW - membranous nephropathy

U2 - 10.1016/j.ekir.2021.02.025

DO - 10.1016/j.ekir.2021.02.025

M3 - Article

C2 - 34169208

VL - 6

SP - 1669

EP - 1676

JO - Kidney International Reports

JF - Kidney International Reports

SN - 2468-0249

IS - 6

ER -