KRIT1 mutations in three Japanese pedigrees with hereditary cavernous malformation

Hirota, Kaoru; Akagawa, Hiroyuki; Kikuchi, Asami; Oka, Hideki; Hino, Akihiko; Mitsuyama, Tetsuryu; Sasaki, Toshiyuki; Onda, Hideaki; Kawamata, Takakazu; Kasuya, Hidetoshi

doi:10.1038/hgv.2016.32

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Patients from this family showed a series of clinical symptoms and features, including seizures, language disorders, dyskinesia, and other symptoms resulting from multiple brain lesions and bleeding. In this case, a heterozygous frame-shift mutation, which has been reported by several times in other countries in the past ( 22 – 25 ), was found in exon 14 (c.1362_1363del) of CCM1 . This single-stranded deletion was predicted to cause coding disorder of amino acid Gln at position 455, leading to premature appearance of stop codons, making the encoded protein truncated and losing normal function.…”

Section: Discussionsupporting

confidence: 63%

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature

Liu

et al. 2022

Front. Neurol.

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BackgroundFamilial cerebral cavernous malformation (FCCM) is a vascular malformation disease closely linked to three identified genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Over the past decade, a few cases of cerebral cavernous malformation (CCM) caused by different gene mutations have been reported in Chinese families. Herein, we introduce a Chinese family affected by FCCM due to a kind of KRIT1/CCM1 frameshift mutation. At the same time, a literature review was conducted to identify case reports of familial cerebral cavernous malformation.Case presentationThe proband in the family in question demonstrated a series of clinical symptoms and features, including headache and bleeding. The proband was hospitalized for headache twice and, both times was examined under suspicion of CCM and received surgical treatment. Magnetic resonance imaging results showed that the proband had multiple intracranial vascular lesions, including on the brain, brainstem, and cerebellum. Genetic test results showed that the classic KRIT1 gene in the proband had a pathogenic mutation. The family members of the proband also showed typical cerebral cavernous malformation when considering clinical manifestations, magnetic resonance imaging findings and genetic test results.ConclusionsWe report a case of Chinese FCCM and its associated symptoms with CCM1-deletion mutations in China. Our findings deepen our understanding of CCM mutations and related phenotypes, the investigation results of this clinical experiment further show that the gene mutation form we reported plays an important role in human FCCM, and this trial investigation is beneficial for genetic counseling for CCM patients.

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Section: Discussionsupporting

confidence: 63%

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature

Liu

et al. 2022

Front. Neurol.

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“…The biochemical connections between these suggest that certain therapies may be effective in multiple types of VMs. The study of abnormal proteins could facilitate the understanding of the molecular mechanisms present in the case of VMs [ 8 , 10 , 11 ].…”

Section: Discussion and Future Therapeutic Perspectives Correlated Wi...mentioning

confidence: 99%

“…All the mutations identified in the CCM genes are LOF mutations, which cause a deficiency of the encoded proteins, causing molecular disorganization and dysfunction of endothelial junctions, affecting the maintenance of the integrity of the vascular barrier. KRIT1 (CCM1) mutations were detected most frequently in patients with HCCVM [ 8 , 10 ]. Recently, somatic mutations of the MAP3K3, PIK3CA, MAP2K7 genes have been identified in CCM lesions, which would suggest that in the case of CCMs there may also be somatic mosaicism [ 13 ].…”

Section: Vascular Anomalies: Ras/raf/mapk/erk Signaling Pathways (Ras...mentioning

confidence: 99%

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Butnariu

Gorduza

Florea

et al. 2022

IJMS

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Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.

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A comparative analysis of the modified Rankin Scale, Karnofsky Performance Status and Kurtzke expanded disability status scale in the perioperative management of patients with brainstem cavernous malformations

Goto

Hino

Hashimoto

2021

Clinical Neurology and Neurosurgery

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KRIT1 mutations in three Japanese pedigrees with hereditary cavernous malformation

Cited by 3 publications

References 22 publications

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

A comparative analysis of the modified Rankin Scale, Karnofsky Performance Status and Kurtzke expanded disability status scale in the perioperative management of patients with brainstem cavernous malformations

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