scholarly journals The Genetic Basis of Moyamoya Disease

2021 ◽  
Author(s):  
R. Mertens ◽  
M. Graupera ◽  
H. Gerhardt ◽  
A. Bersano ◽  
E. Tournier-Lasserve ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Cerebral Angiography ◽  
Genetic Basis ◽  
Age Of Onset ◽  
Gene Dosage ◽  
Cerebral Arteries ◽  
Susceptibility Gene ◽  
Neurological Dysfunction ◽  
Individual Risk ◽  
Rnf213 Gene

AbstractMoyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a “puff of smoke” (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the  development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

scholarly journals Experimental animal models for moyamoya disease and treatment: a pathogenesis-oriented scoping review

2021 ◽  
Vol 51 (3) ◽  
pp. E5
Author(s):  
Michael S. Rallo ◽  
Omar Akel ◽  
Akhilesh Gurram ◽  
Hai Sun
Keyword(s):  
Animal Models ◽  
Experimental Animal ◽  
Moyamoya Disease ◽  
Scoping Review ◽  
Carotid Arteries ◽  
Data Extraction ◽  
Cerebral Arteries ◽  
Susceptibility Gene ◽  
Cerebral Hypoperfusion ◽  
Experimental Animal Models

OBJECTIVE Moyamoya disease (MMD) is an intracranial steno-occlusive pathology characterized by progressive narrowing of proximal large vessels, including the terminal internal carotid arteries (ICAs), middle cerebral arteries, or anterior cerebral arteries. Named for the “puff of smoke” appearance of the anomalous vascularization visualized on cerebral angiography, MMD lacks a well-defined etiology, although significant insights have been made, including the identification of a susceptibility gene, RNF213, in humans with the disease. A limitation to advancing the understanding and treatment of MMD has been the lack of experimental animal models that authentically reflect the clinical pathogenesis. In an effort to analyze characteristics of currently available models and identify strategies for future model generation, the authors performed a scoping review of experimental animal models that have been used to study MMD. METHODS A systematic search of PubMed, Web of Science, and Scopus was performed to identify articles describing animal models used to study MMD. Additional articles were identified via citation searching. Study selection and data extraction were performed by two independent reviewers based on defined inclusion and exclusion criteria. RESULTS A total of 44 articles were included for full-text review. The methods used to generate these animal models were broadly classified as surgical (n = 25, 56.8%), immunological (n = 7, 15.9%), genetic (n = 6, 13.6%), or a combination (n = 6, 13.6%). Surgical models typically involved permanent ligation of one or both of the common carotid arteries or ICAs to produce chronic cerebral hypoperfusion. Genetic models utilized known MMD or cerebrovascular disease-related genes, such as RNF213 or ACTA2, to induce heritable cerebral vasculopathy. Finally, immunological models attempted to induce vasculitis-type pathology by recapitulating the inflammatory milieu thought to underlie MMD. CONCLUSIONS Models generated for MMD have involved three general approaches: surgical, immunological, and genetic. Although each reflects a key aspect of MMD pathogenesis, the failure of any individual model to recapitulate the development, progression, and consequences of the disease underscores the importance of future work in developing a multietiology model.

Abstract TP448: Genome-wide CNV Array Analysis Following Post-hoc Targeted Amplicon Sequencing Revealed Genetic Anticipation in Parent-offspring Pairs with Moyamoya Disease

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Masaki Ito ◽  
Haruto Uchino ◽  
Ken Kazumata ◽  
Yuuka Hama ◽  
Shuji Hamauchi ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Age Of Onset ◽  
Gene Dosage ◽  
Age At Onset ◽  
Amplicon Sequencing ◽  
Oligonucleotide Array ◽  
Copy Number Loss ◽  
Genome Wide

Introduction: Molecular mechanisms underlying clinical observation of progressively earlier age of onset of Moyamoya disease (MMD) as it is passed on to the next generation, as known as clinical anticipation, is still obscure. This study investigates copy number variation (CNV) in parent-offspring pairs with MMD with and without clinical anticipation using genome-wide CNV array following high-throughput DNA sequencing. Methods: Fifteen out of 25 consecutive Japanese parent-offspring pairs with MMD treated at our institute since 1980 were enrolled. Demographics, inheritance pattern, angiographical stage, disease type at onset were reviewed. Using genomic DNA from whole blood, rs112735431 in RNF213 gene was genotyped, then genome-wide CNV analysis was conducted using a 2.6 M oligonucleotide array to compare CNV profile in parent-offspring pairs with and without clinical anticipation. Amplicon Sequencing was further conducted using Miseq. Results: Clinical anticipation was observed in 10 pairs (67%) and was not in 5 pairs (33%). In clinical anticipation group, mean age at onset was significantly lower in the offsprings than in the parents (p<0.001). There were no significant differences in other clinical and genetic backgrounds, including the genotype in RNF213 between the generations and between the groups with and without clinical anticipation. Genome-wide CNV profiling revealed that 10 CNV in chr7q, 8p, 9q, 14q, 16p, 19p, 20q, and 22q were overlapped for more than 3 individuals in the whole studied population. Of these CNV, copy number was different only in chr16p13.3 between the generations in clinical anticipation group (P=0.06). Fourteen genes were observed in this locus, including GNPTG gene, whose mutation is known to be associated with mucolipidosis. Amplicon sequence targeting these 14 genes revealed significant copy number loss at GNPTG gene locus, in the offsprings compared to their parent (P = 0.02, copy number = 1.8 and 2.0, respectively). Conclusion: These data suggest clinical anticipation of MMD in Japanese population can be observed regardless of the RNF213 genotype. This is the first genome-wide CNV profiling, suggesting the CNV in chr16p13.3 might be underlying mechanism for anticipation in familial MMD by reducing gene dosage.

scholarly journals Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

2016 ◽  
Vol 41 (3-4) ◽  
pp. 105-118 ◽  
Author(s):  
Anna Bersano ◽  
Stephanie Guey ◽  
Gloria Bedini ◽  
Sara Nava ◽  
Dominique Hervé ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Genetic Factors ◽  
Age Of Onset ◽  
Biological Fluids ◽  
Tailored Interventions ◽  
Asian Patients ◽  
Independent Series ◽  
Inflammatory Molecules ◽  
Rnf213 Gene

Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

DIFFICULTIES IN DIAGNOSING MOYA-MOYA DISEASE (CLINICAL CASE)

2020 ◽  
pp. 48-53
Author(s):  
Novikova I.N. ◽  
Popova T.F. ◽  
Gribacheva I.A. ◽  
Petrova E.V. ◽  
Marushchak A.A. ◽  
...  
Keyword(s):  
Cerebral Angiography ◽  
Neurological Disorders ◽  
Clinical Case ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
Cerebral Arteries ◽  
Moya Moya Disease ◽  
Middle Cerebral Arteries ◽  
Internal Carotid Arteries ◽  
Made In

Moya-Moya disease is a rare progressive chronic cer-ebrovascular disease characterized by a narrowing of the lumen of the intracranial segments of the internal carotid arteries, as well as the initial segments of the anterior and middle cerebral arteries with the devel-opment of a network of small vascular anastomoses. Violations of blood supply due to occlusion lead to the development of ischemic strokes in the correspond-ing pools, and ruptures of vascular anastomoses - to the development of hemorrhagic strokes, causing a variety of neurological disorders. The article presents a clinical case of Moya-Moya disease in a 31-year-old patient. The disease was manifested by acute disorders of cerebral circulation in ischemic and hemorrhagic types. The diagnosis was made in accordance with the diagnostic criteria of the disease based on the data of endovascular cerebral angiography.

scholarly journals Hyperhomocysteinemia in a Patient with Moyamoya Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Durga Shankar Meena ◽  
Gopal Krishana Bohra ◽  
Mahadev Meena ◽  
Bharat Kumar Maheshwari
Keyword(s):  
Cerebrovascular Disease ◽  
Moyamoya Disease ◽  
Cerebral Angiography ◽  
Rare Case ◽  
Homocysteine Level ◽  
Case Reports ◽  
Circle Of Willis

Moyamoya disease is a chronic progressive cerebrovascular disease characterized by bilateral occlusion or stenosis of arteries around circle of Willis. We report a case of 18-year-old female presented with recurrent episodes of headache and vertigo. On cerebral angiography, the patient was diagnosed to have moyamoya disease. On further evaluation, thrombophilia profile showed increased homocysteine level. The patient was treated conservatively with cobalamin and aspirin and advised for revascularization. According to the literature, there are few case reports of moyamoya disease with thrombotic disorders. Hence, we are reporting this interesting and rare case.

Radionuclide Cerebral Angiography in Moyamoya Disease

1979 ◽  
Vol 4 (12) ◽  
pp. 513-515
Author(s):  
TOSHIO MAEDA ◽  
HIROFUMI MORI ◽  
KINICHI HISADA ◽  
MINORU SUGINO
Keyword(s):  
Moyamoya Disease ◽  
Cerebral Angiography

scholarly journals THE GENETIC BASIS OF DOSAGE COMPENSATION OF ALCOHOL DEHYDROGENASE-1 IN MAIZE

Genetics ◽  
1981 ◽  
Vol 97 (3-4) ◽  
pp. 625-637 ◽  
Author(s):  
James A Birchler
Keyword(s):  
Alcohol Dehydrogenase ◽  
Structural Gene ◽  
Dosage Compensation ◽  
Genetic Basis ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Gene Dosage Effect ◽  
Negative Effect ◽  
Higher Eukaryotes ◽  
Alcohol Dehydrogenase 1

ABSTRACT The levels of alcohol dehydrogenase (ADH) do not exhibit a structural gene-dosage effect in a one to four dosage series of the long arm of chromosome one (1L) (BIRCHLER19 79). This phenomenon, termed dosage compensation, has been studied in more detail. Experiments are described in which individuals aneuploid for shorter segments were examined for the level of ADH in order to characterize the genetic nature of the compensation. The relative ADH expression in segmental trisomics and tetrasomics of region IL 0.72–0.90, which includes the Adh locus, approaches the level expected from a strict gene dosage effect. Region IL 0.20–0.72 produces a negative effect upon ADH in a similar manner to that observed with other enzyme levels when IL as a whole is varied (BIRCHLEF1I9 79). These and other comparisons have led to the concept that the compensation of ADH results from the cancellation of the structural gene effect by the negative aneuploid effect. The example of ADH is discussed as a model for certain other cases of dosage compensation in higher eukaryotes.

scholarly journals A case of Young Stroke due to Moyamoya Disease

2020 ◽  
Vol 15 (1) ◽  
pp. 110-113
Author(s):  
Md Abdur Razzak ◽  
Ghulam Kawnayn ◽  
Fateha Naznin ◽  
Quazi Audry Arafat Rahman
Keyword(s):  
Moyamoya Disease ◽  
Past History ◽  
Cerebral Arteries ◽  
Armed Forces ◽  
Cerebral Angiogram ◽  
Medical College ◽  
Middle Cerebral Arteries ◽  
History Of ◽  
Collateral Vessels ◽  
The Right

Moyamoya disease is a disease in which certain arteries in the brain are constricted. Blood flow is blocked by the constriction, and also by blood clots (thrombosis). A collateral circulation develops around the blocked vessels to compensate for the blockage, but the collateral vessels are small, weak, and prone to bleeding, aneurysm and thrombosis which may result in TIA, recurrent ischemic or hemorrhagic stroke or seizure. The disease may manifest in pediatric age or young adults. In May 2019 we have diagnosed a young lady with Moyamoya disease who presented with right sided hemiplegia, motor aphasia and dysphagia. She was labeled as hypertensive 6 months prior to this event and used to take anti-hypertensive irregularly and gave past history of occasional headache. Her CT scan and MRI of brain revealed left sided ischemic infarct involving frontotemporoparietal region and cerebral angiogram revealed narrowing of left MCA and non-visualization of distal part. There is extensive fine collaterals (Moyamoya vessels) giving the appearance of puffed smoke. The right ACA and MCA were also narrowed with appearance of early collateral vessels. She was treated with aspirin, PPI, NG feeding, antihypertensive medication, physiotherapy, rehabilitation therapy and other supportive care. His condition gradually improved and discharged on 2.7.19. He was referred to Department of Neurosurgery for cerebral revascularization by STA-MCA (superficial temporal and middle cerebral arteries) bypass surgery after stabilization and MR perfusion study. Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 110-113

Unilateral sudden hearing loss as the first presenting symptom of moyamoya disease

2013 ◽  
Vol 127 (2) ◽  
pp. 196-199 ◽  
Author(s):  
L-S Tseng ◽  
S-D Luo
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Moyamoya Disease ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
Cerebral Arteries ◽  
Sudden Onset ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Internal Carotid Arteries

AbstractObjective:We describe a rare case of sudden onset of unilateral sensorineural hearing loss occurring as the first symptom of moyamoya disease, which is characterised by progressive stenosis of the intracranial internal carotid arteries and their proximal anterior cerebral arteries and middle cerebral arteries.Method:Case report and review of the world literature regarding moyamoya disease with hearing loss.Results:The reported patient had moyamoya disease that initially presented as sudden, unilateral sensorineural hearing loss. Magnetic resonance imaging showed occlusion of the anterior cerebral, middle cerebral and distal internal carotid arteries bilaterally. The possible mechanism of this patient's sudden sensorineural hearing loss may have been vascular occlusion resulting from thrombotic narrowing or blockage by plaque.Conclusion:The described patient represents the first reported case of sudden onset, unilateral sensorineural hearing loss occurring as the first symptom of moyamoya disease. The possibility of a vascular lesion such as moyamoya disease should be considered in patients with sudden sensorineural hearing loss, especially children, young adults and Asian patients. Due to this disease's poor outcome, early diagnosis and treatment are important to prevent stroke.

Sign in / Sign up

Export Citation Format

Share Document