Related Experiment Video
Updated: Mar 13, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Moyamoya vasculopathy shows a genetic mutational gradient decreasing from East to West
Alessandro Raso1, Roberto Biassoni2, Samantha Mascelli2
1Unit of Neurosurgery, Giannina Gaslini Institute, Genoa, Italy - rasoale@yahoo.it.
Background:
Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid arteries and an abnormal vascular network at the base of the brain determining stroke in children. Patients with a similar vasculopathy and associated conditions are affected by the moyamoya syndrome (MMS). Most of the studies focused on MMD were carried out on East-Asian population. Ring Finger 213 (RNF213) has been identified as the strongest susceptibility gene for MMD in East-Asian people. Overall, 74.5% of the East-Asian patients carry the founder variant p.Arg4810Lys of RNF213 never reported in Caucasians. A different genetic landscape among the diverse ethnic populations seems to exist.
Methods:
We sequenced the coding sequence region of RNF213, TGFB1 and PDGFRB in 21 ethnically homogeneous Italian children with moyamoya; comprehensive sequencing data are available from parents of eight of them. The analyses were carried out by NGS on Thermo-fisher PGM platform. We also performed a comprehensive review of the literature about the variations of these three genes in Caucasian patients.
Results:
Several new variants of RNF213 gene were detected, in particular, two new pathogenic mutations on RNF213 (p.Trp4677Leu and p.Cys4017Ser) were identified in one MMS case and in one MMD case, respectively. Moreover, in a MMS case a new probably causing disease mutation p.Pro1063Thr of PDGFRB was detected.
Conclusions:
The genetic susceptibility of Asian moyamoya vasculopathy seems to differ from the Caucasian disease. No additional differences seem to exist between MMD and MMS.
Insights
Genetic analysis in Italian children reveals distinct moyamoya disease (MMD) and moyamoya syndrome (MMS) gene variants compared to East Asian populations. New mutations in RNF213 and PDGFRB were identified in Caucasian patients.
Area of Science:
- Genetics
- Neurology
- Cerebrovascular Diseases
Background:
- Moyamoya disease (MMD) and moyamoya syndrome (MMS) are cerebrovascular conditions causing stroke, particularly in children.
- Most research on MMD genetics focuses on East Asian populations, identifying RNF213 as a key susceptibility gene.
- The founder variant p.Arg4810Lys in RNF213 is prevalent in East Asians but absent in Caucasians, suggesting ethnic differences in genetic predisposition.
Purpose of the Study:
- To investigate the genetic landscape of MMD and MMS in a Caucasian (Italian) pediatric cohort.
- To identify novel genetic variants in RNF213, TGFB1, and PDGFRB associated with moyamoya vasculopathy in non-Asian populations.
- To compare genetic findings between MMD and MMS and across different ethnic groups.
Main Methods:
- Sequencing of the coding regions of RNF213, TGFB1, and PDGFRB genes in 21 Italian children with MMD/MMS.
- Utilizing Next-Generation Sequencing (NGS) on the Thermo-fisher PGM platform.
- Performing a comprehensive literature review of gene variations in Caucasian moyamoya patients.
Main Results:
- Identification of several novel RNF213 variants.
- Discovery of two new pathogenic mutations in RNF213 (p.Trp4677Leu and p.Cys4017Ser) in one MMS and one MMD case, respectively.
- Detection of a new likely pathogenic mutation in PDGFRB (p.Pro1063Thr) in one MMS case.
Conclusions:
- The genetic basis of moyamoya vasculopathy in Caucasian populations differs from that in Asian populations.
- No significant genetic distinctions were observed between MMD and MMS in this study.
- These findings highlight the importance of ethnic diversity in understanding the genetic architecture of moyamoya disease.
More Related Videos
07:15Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Related Concept Videos
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
02:59Animal Mitochondrial Genetics
01:27Principles of Pharmacogenetics: Types of Genetic Variants
01:31Translation
Translation Produces the Building Blocks of Life
Proteins are...
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
01:30Point and Frameshift Mutations