Improving clinical interpretation of five KRIT1 and PDCD10 intronic variants.
Clin Genet
; 99(6): 829-835, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33604894
ABSTRACT
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 Here, the mRNA analysis for two intronic unpublished variants (KRIT1 c.1147-7 T 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Proteínas Reguladoras de Apoptose
/
Proteína KRIT1
/
Proteínas de Membrana
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália