Downie, ML;
Gupta, S;
Tekman, MC;
Cheshire, C;
Arora, S;
Licht, C;
Robinson, LA;
... Kleta, R; + view all
(2021)
Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy.
Kidney International Reports
10.1016/j.ekir.2021.02.025.
(In press).
Preview |
Text
Gale_1-s2.0-S2468024921000966-main.pdf - Published Version Download (768kB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ekir.2021.02.025 |
| Publisher version: | https://doi.org/10.1016/j.ekir.2021.02.025 |
| Language: | English |
| Additional information: | © 2021 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Genetic risk score; glomerulonephritis; linkage analysis; LOD score; membranous nephropathy; X-linked |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10125981 |
Loading...
Loading...Loading...| 1. |  United States | 7 |
| 2. |  Germany | 6 |
| 3. |  Canada | 3 |
| 4. |  China | 3 |
| 5. |  Switzerland | 1 |
| 6. |  Russian Federation | 1 |
| 7. |  Turkey | 1 |
Archive Staff Only
 |
View Item |
