Digenic Alport Syndrome
Por:
Savige, J, Renieri, A, Ars, E, Daga, S, Pinto, AM, Rothe, H, Gale, DP, Aksenova, M, Cerkauskaite, A, Bielska, O, Lipska-Zietkiewicz, B, Gibson, JT
Publicada:
1 nov 2022
Ahead of Print:
1 jun 2022
Resumen:
Digenic Alport syndrome refers to the inheritance of pathogenic variants in COL4A5 plus COL4A3 or COL4A4 or in COL4A3 plus COL4A4. Where digenic Alport syndrome includes a pathogenic COL4A5 variant, the consequences depend on the sex of the affected individual, COL4A5 variant ?severity,? and the nature of the COL4A3 or COL4A4 change. A man with a pathogenic COL4A5 variant has all his collagen IV ?3?4?5-heterotrimers affected, and an additional COL4A3 or COL4A4 variant may not worsen disease. A woman with a pathogenic COL4A5 variant has on average 50% of her heterotrimers affected, which is increased to 75% with a further COL4A3 or COL4A4 variant and associated with a higher risk of proteinuria. In digenic Alport syndrome with pathogenic COL4A3 and COL4A4 variants, 75% of the heterotrimers are affected. The COL4A3 and COL4A4 genes occur head-to-head on chromosome 2, and inheritance is autosomal dominant when both variants affect the same chromosome (in cis) or recessive when they affect different chromosomes (in trans). This form of digenic disease results in increased proteinuria and a median age of kidney failure intermediate between autosomal dominant and autosomal recessive Alport syndrome. Previous guidelines have suggested that all pathogenic or likely pathogenic digenic variants should be identified and reported. Affected family members should be identified, treated, and discouraged from kidney donation. Inheritance within a family is easier to predict if the two variants are considered independently and if COL4A3 and COL4A4 variants are known to be inherited on the same or different chromosomes.
Filiaciones:
Savige, J:
Univ Melbourne, Dept Med Melbourne Hlth & Northern Hlth, Parkville, Vic, Australia
Univ Melbourne, Royal Melbourne Hosp, Dept Med Melbourne Hlth & Northern Hlth, 300 Grattan St, Parkville, VIC 3050, Australia
Renieri, A:
Univ Siena, Med Genet Unit, Siena, Italy
Univ Siena, Med Biotech Hub & Competence Ctr, Dept Med Biotechnol, Siena, Italy
Azienda Osped Univ Senese, Genet Med, Siena, Italy
Ars, E:
Univ Autonomade Barcelona, Dept Nephrol, Mol Biol Lab, Fundacio Puigvert,Inst Invest Biomed Sant Pau, Barcelona, Spain
Daga, S:
Univ Siena, Med Genet Unit, Siena, Italy
Univ Siena, Med Biotech Hub & Competence Ctr, Dept Med Biotechnol, Siena, Italy
Pinto, AM:
Azienda Osped Univ Senese, Genet Med, Siena, Italy
Rothe, H:
Ctr Nephrol & Metab Disorders, Weisswasser, Germany
Gale, DP:
UCL, Dept Renal Med, London, England
Aksenova, M:
Pirogov Russian Natl Res Med Univ, Veltischev Res & Clin Inst Pediat, Dept Nephrol, Moscow, Russia
Cerkauskaite, A:
Vilnius Univ, Inst Biomed Sci, Div Diagnost & Treatment Rare Kidney & Metab Dis, Vilnius, Lithuania
Bielska, O:
Med Univ Gdansk, Ctr Rare Dis, Gdansk, Poland
Med Univ Gdansk, Clin Genet Unit, Gdansk, Poland
Lipska-Zietkiewicz, B:
Med Univ Gdansk, Ctr Rare Dis, Gdansk, Poland
Med Univ Gdansk, Clin Genet Unit, Gdansk, Poland
Gibson, JT:
Univ Melbourne, Dept Med Melbourne Hlth & Northern Hlth, Parkville, Vic, Australia
Open Access
|