De novo mutations in CBL causing early-onset paediatric moyamoya angiopathy

Guey, Stéphanie; Grangeon, Lou; Brunelle, Françis; Bergametti, Françoise; Amiel, Jeanne; Lyonnet, Stanislas; Delaforge, Audrey; Arnould, Minh; Desnous, Béatrice; Bellesme, Céline; Hervé, Dominique; Schwitalla, Jan Claudius; Kraemer, Markus; Tournier‐Lasserve, Elisabeth; Kossorotoff, Manoëlle

doi:10.1136/jmedgenet-2016-104432

Cited by 35 publications

(25 citation statements)

References 33 publications

(16 reference statements)

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“…Eleven patients harbored splicesite mutations, located at intron 7 or 9, causing in-frame deletions of the RING finger domain responsible for the E3 ubiquitin ligase activity. 2,[10][11][12][13] Nine of these patients developed JMML, and 78% (n = 7) required HSCT. All JMML cases with the c.1228-2A>G mutation underwent HSCT, in contrast with those with splice-site mutations on intron 7, 50% of whom underwent HSCT, suggesting that a splice-site mutation located at intron 7 could be associated with a favorable outcome (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Castro

Galán-Gómez

Corral-Sánchez

et al. 2021

Clinical Case Reports

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Section: Discussionmentioning

confidence: 99%

Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Castro

Galán-Gómez

Corral-Sánchez

et al. 2021

Clinical Case Reports

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“…In addition, syndromic MMD displaying X-linked recessive inheritance [169] has been associated with loss of BRCC3 (Xq28), a gene essential for angiogenesis [170]. Finally, MMD with no strictly defined pattern of inheritance has been associated with numerous other loci [171-176]. The most recently identified candidate gene, CCER2 on chromosome 19, has been proposed as a potential biomarker of MMD due to brain-specific expression [177].…”

Section: Hereditary Hemorrhagic Cerebrovascular Diseasementioning

confidence: 99%

Cerebrovascular disorders associated with genetic lesions

Karschnia

Nishimura

Louvi

2018

Cell. Mol. Life Sci.

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Cerebrovascular disorders are underlain by perturbations in cerebral blood flow and abnormalities in blood vessel structure. Here we provide an overview of current knowledge of select cerebrovascular disorders that are associated with genetic lesions and connect genomic findings with analyses aiming to elucidate the cellular and molecular mechanisms of disease pathogenesis. We argue that a mechanistic understanding of genetic (familial) forms of cerebrovascular disease is a prerequisite for the development of rational therapeutic approaches, and has wider implications for treatment of sporadic (non-familial) forms, which are usually more common.

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“…Several MMS causative genes have been identified, including genes involved in the RAS, genomic maintenance or NO pathways 6. Most variants already identified are single nucleotide variations 9–12. A few cytogenetic anomalies have also been reported in a limited number of patients 13–20.…”

Section: Introductionmentioning

confidence: 99%

Xq28 copy number gain causing moyamoya disease and a novel moyamoya syndrome

et al. 2020

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BackgroundThe molecular anomalies causing moyamoya disease (MMD) and moyamoya syndromes (MMS) are unknown in most patients.ObjectiveThis study aimed to identify de novo candidate copy number variants (CNVs) in patients with moyamoya.MethodsRare de novo CNVs screening was performed in 13 moyamoya angiopathy trios using whole exome sequencing (WES) reads depth data and whole genome high density SNP array data. WES and SNP array data from an additional cohort of 115 unrelated moyamoya probands were used to search for recurrence of these rare de novo CNVs.ResultsTwo de novo CNVs were identified in two unrelated probands by both methods and confirmed by qPCR. One of these CNVs, located on Xq28, was detected in two additional families. This interstitial Xq28 CNV gain is absent from curated gold standard database of control genomic variants and gnomAD databases. The critical region contains five genes, including MAMLD1, a major NOTCH coactivator. Typical MMD was observed in the two families with a duplication, whereas in the triplicated patients of the third family, a novel MMS associating moyamoya and various systemic venous anomalies was evidenced.ConclusionThe recurrence of this novel Xq28 CNV, its de novo occurrence in one patient and its familial segregation with the affected phenotype in two additional families strongly suggest that it is pathogenic. In addition to genetic counselling application, its association with pulmonary hypertension is of major importance for clinical care. These data also provide new insights into the genomic architecture of this emblematic, non-atherosclerotic, large vessel disease.

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De novo mutations in CBL causing early-onset paediatric moyamoya angiopathy

Abstract: These data suggest that gene screening should be considered in early-onset moyamoya, even in the absence of obvious signs of RASopathy.

Cited by 35 publications

References 33 publications

Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Cerebrovascular disorders associated with genetic lesions

Xq28 copy number gain causing moyamoya disease and a novel moyamoya syndrome

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