Improving clinical interpretation of five KRIT1 and PDCD10 intronic variants
| Autor: | Marco Castori, Marilena Carmela Di Giacomo, Leonardo D'Agruma, Grazia Nardella, Antonio Petracca, Carmela Fusco, Stefano Gambardella, Stefania Zampatti, Nicola Paciello, Silvia Lanfranconi, Lucia Micale, Dario Ronchi |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Hemangioma Cavernous Central Nervous System Vascular homeostasis KRIT1 In silico PDCD10 RNA Splicing Central nervous system Complex formation 030105 genetics & heredity Biology Frameshift mutation cerebral cavernous malformations 03 medical and health sciences splicing Proto-Oncogene Proteins Genetics medicine Humans mRNA analysis RNA Messenger KRIT1 Protein Genetics (clinical) Messenger RNA Vascular malformation Membrane Proteins medicine.disease 030104 developmental biology medicine.anatomical_structure RNA splicing Mutation Apoptosis Regulatory Proteins |
| Zdroj: | Clinical geneticsREFERENCES. 99(6) |
| ISSN: | 1399-0004 |
| Popis: | Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system which may occur sporadically or segregate within families due to heterozygous variants in KRIT1/CCM1, MGC4607/CCM2 or PDCD10/CCM3. Intronic variants are not uncommon in familial CCM, but their clinical interpretation is often hampered by insufficient data supporting in silico predictions. Here, the mRNA analysis for two intronic unpublished variants (KRIT1 c.1147-7 T > G and PDCD10 c.395 + 2 T > G) and three previously published variants in KRIT1 but without data supporting their effects was carried out. This study demonstrated that all variants can induce a frameshift with the lack of residues located in the C-terminal regions and involved in protein-protein complex formation, which is essential for vascular homeostasis. These results support the introduction of mRNA analysis in the diagnostic pathway of familial CCM and expand the knowledge of abnormal splicing patterning in this disorder. |
| Databáze: | OpenAIRE |
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