Tambala, Diana;
Vassar, Rachel;
Snow, John;
Balestrini, Simona;
Bersano, Anna;
Guey, Stéphanie;
Bonaventura, Eleonora;
... Musolino, Patricia L; + view all
(2025)
COL4A1 and COL4A2-Related Disorders - Clinical Features, Diagnostic Guidelines, and Management.
Genetics in Medicine
, 27
(9)
, Article 101514. 10.1016/j.gim.2025.101514.
Preview |
Text
Balestrini_1-s2.0-S1098360025001613-main.pdf Download (476kB) | Preview |
Abstract
Purpose: Collagen type 4 alpha 1 (COL4A1) and alpha 2 (COL4A2) chains, encoded byCOL4A1 and COL4A2, are essential for basement membrane integrity, contributing to structural stability and cell regulation. Pathogenic variants in these genes cause a spectrum of autosomal dominant and, more rarely, autosomal recessive disorders, which are collectively known as COL4A1/A2-related disorders. These multisystem disorders can include neurologic, ophthalmologic, renal, and other organ system pathology and vary widely in symptoms, complicating diagnosis and management. Methods: Using a modified eDelphi method, we obtained consensus from international experts across medical subspecialties on the evaluation and management of COL4A1/A2-related disorders, with consensus set at ≥70% agreement. Results: Consensus was achieved on recommendations for evaluating and managing these conditions. Conclusion: Genetic testing and counseling are advised for individuals showing symptoms of COL4A1/A2-related disorders and for at-risk relatives. Given the complexity and rarity of these disorders, management requires a multidisciplinary approach informed by current understanding of disease mechanisms. Recommended care includes neurological and ophthalmological imaging and monitoring of cardiovascular and renal function. Ongoing research is critical to uncover genotype-phenotype links and potential modifiers, with clinical research participation encouraged to advance knowledge and treatments.
| Type: | Article |
|---|---|
| Title: | COL4A1 and COL4A2-Related Disorders - Clinical Features, Diagnostic Guidelines, and Management |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.gim.2025.101514 |
| Publisher version: | https://doi.org/10.1016/j.gim.2025.101514 |
| Language: | English |
| Additional information: | © 2025 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | COL4A1, COL4A2, Delphi, Genotype-phenotype, Guidelines |
| 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 Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211010 |
Archive Staff Only
 |
View Item |
