{"id":4417,"date":"2024-06-15T08:37:21","date_gmt":"2024-06-15T08:37:21","guid":{"rendered":"https:\/\/www.col4a1.net\/?p=4417"},"modified":"2024-06-16T20:08:30","modified_gmt":"2024-06-16T20:08:30","slug":"molecular-genetics-of-all-known-col4a1-a2-disease","status":"publish","type":"post","link":"https:\/\/www.col4a1.net\/en\/molecular-genetics-of-all-known-col4a1-a2-disease\/","title":{"rendered":"Molecular genetics of all known COL4A1-A2 disease"},"content":{"rendered":"

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Molecular genetics of all known COL4A1-A2 disease<\/h1>\n<\/div>
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Dr. Elisabeth Tournier Lasserve, from the Service of Molecular Neurovascular Genetics, Saint-Louis Hospital, Paris and University of Paris, INSERM, Paris, France, in her presentation titled “Molecular genetics of all known COL4A1\/COL4A2 diseases,” thanked the Association for the important moment of discussion. She focused on the genetic mutations associated with known COL4A1\/COL4A2 diseases.<\/p>\n

Dr. Tournier Lasserve explained that various types of mutations affect the COL4A1 and COL4A2 genes, each leading to different effects on the corresponding proteins.<\/p>\n

Missense mutations are one of the main types discussed. These mutations involve the substitution of one amino acid for another in the protein sequence. When it concerns glycine residues in the Gly-X-Y motif present in the triple helix portion of the protein, the resulting mutated protein cannot be properly secreted into the cell matrix, causing toxic effects on the cell.<\/p>\n

Another type of mutation discussed is the premature stop codon. A stop codon is an information unit in the genetic code, consisting of a sequence of three nucleotides in DNA and the corresponding messenger RNA, which serves as a signal to stop reading and indicates that protein production is complete. In this case, the DNA sequence contains an erroneous stop signal, leading to the production of an incomplete and therefore non-functional protein. Insufficient production of the protein can have serious repercussions on the patient’s health.<\/p>\n

Dr. Tournier Lasserve also mentioned the PADMAL mutation and the duplications or triplications of the COL4A1\/COL4A2 genes. In both cases, these mutations lead to an increased regulation of these genes, causing a pathological mechanism very different from stop codon mutations. In fact, there is what is called the upregulation of COL4A1\/A2, which results in an increase in the amount of protein produced, potentially causing a functional and pathological overload of the cells.<\/p>\n

During her presentation, Dr. Tournier Lasserve illustrated these concepts with various clinical examples, showing how different mutations can manifest differently in patients. Each example highlighted the specific consequences of the mutations on the COL4A1 and COL4A2 proteins, emphasizing the importance of accurate diagnosis and a detailed understanding of the mutations for effective treatment of related diseases.<\/p>\n

In France, all patients with cerebral small vessel disease (CSVD) report to their medical center, and between 2016 and 2020, they received more than 3000 patients, 80% of whom were adults and 20% children or fetuses. Genetic analysis of these patients revealed that 1.6% had mutations in the COL4A1 or COL4A2 genes, particularly glycine missense mutations or stop codon mutations. These mutations are associated with a range of symptoms with highly variable phenotypes. In addition to neurological manifestations such as brain haemorrhages, vascular leukoencephalopathies, and retinal artery tortuosity, there can also be a series of extra-neurological manifestations, including:<\/p>\n