Back to Search
Start Over
Improving clinical interpretation of five KRIT1 and PDCD10 intronic variants
- Source :
- Clinical geneticsREFERENCES. 99(6)
- Publication Year :
- 2021
-
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 Here, the mRNA analysis for two intronic unpublished variants (KRIT1 c.1147-7 T 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 13990004
- Volume :
- 99
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Clinical geneticsREFERENCES
- Accession number :
- edsair.doi.dedup.....8359f72143dfbe517b14197f8e96362e