Identification of a Locus on the X Chromosome Linked to Familial Membranous Nephropathy
| Autor: | Chris Cheshire, Mallory L. Downie, Alvaro Madrid Aris, Steven Arora, Horia Stanescu, Christoph Licht, Lisa A. Robinson, Robert Kleta, Mehmet Tekman, Paul Brenchley, Sanjana Gupta, Detlef Bockenhauer, Ibrahim Al Attrach, Marina Munoz, Daniel P. Gale |
|---|---|
| Přispěvatelé: | Institut Català de la Salut, [Downie ML] Department of Renal Medicine, University College London, London, UK. Paediatric Nephrology, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, UK. [Gupta S, Cheshire C] Department of Renal Medicine, University College London, London, UK. [Tekman MC] Department of Computer Science, University of Freiburg, Freiburg, Germany. [Arora S] Department of Paediatrics, Division of Nephrology, McMaster Children’s Hospital, Hamilton, Ontario, Canada. [Licht C] Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. [Munoz M] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::enfermedades genéticas ligadas al cromosoma X [ENFERMEDADES]
030232 urology & nephrology Locus (genetics) 030204 cardiovascular system & hematology genetic risk score Cromosoma X 03 medical and health sciences 0302 clinical medicine Membranous nephropathy Clinical Research Genetic linkage Polymorphism (computer science) Other subheadings::Other subheadings::/genetics [Other subheadings] medicine enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::nefritis::glomerulonefritis::glomerulonefritis membranosa [ENFERMEDADES] linkage analysis Glomerulonefritis - Aspectes genètics X chromosome X-linked Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Nephritis::Glomerulonephritis::Glomerulonephritis Membranous [DISEASES] Genetics Autosome Otros calificadores::Otros calificadores::/genética [Otros calificadores] business.industry Haplotype membranous nephropathy Chromosome medicine.disease LOD score Diseases of the genitourinary system. Urology Nephrology RC870-923 Malalties congènites Congenital Hereditary and Neonatal Diseases and Abnormalities::Genetic Diseases Inborn::Genetic Diseases X-Linked [DISEASES] business glomerulonephritis |
| Zdroj: | Scientia 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, 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 Kidney International Reports, Vol 6, Iss 6, Pp 1669-1676 (2021) Kidney International Reports |
| ISSN: | 2468-0249 |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|