Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperkeratotic capillary-venous malformations (HCCVMs) are rare cutaneous lesions that occur in a small subgroup of patients with cerebral capillary malformation (CCM). CCMs cause neurological problems that range from headaches to life-threatening intracranial bleeding. CCMs and HCCVMs have a similar histopathological appearance of dilated capillary-venous channels. Genetic linkage of inherited CCMs has been established to three chromosomal loci, 3q25. 2-27, 7p13-15 and 7q21-22. The first mutations were identified in the CCM1 gene (located on 7q21-22), which encodes KRIT1 protein (KREV1 interaction trapped 1), presumably a membrane-bound protein with signalling activity. Although KRIT1 is known to interact with KREV1/RAP1A, a Ras-family GTPase, the exact function of KRIT1 in the formation of cerebral capillaries and veins is poorly understood. In this study, we screened five families with CCM for mutations in the KRIT1 gene. In one of the families, CCMs co-segregated with HCCVMs. We identified a KRIT1Delta(G103)mutation in this family, suggesting that this rare form of the condition is also caused by mutations in the CCM1 gene and that KRIT1 is probably important for cutaneous vasculature. Interestingly, this deletion introduces the earliest stop codon among identified mutations, suggesting a possible correlation between the molecular alteration and the cutaneous phenotype. Another novel mutation, KRIT1(IVS2+2(T-->C)), was found in a family with only cerebral capillary-venous malformations.
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PMID:KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation. 1081 16

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.
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PMID:Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families. 1976 Feb 87

Cerebral cavernous malformations (CCM) commonly known as cavernous hemangioma are associated with abnormally enlarged thin-walled blood vessels. As a result, these dilated capillaries are prone to leakage and result in hemorrhages. Clinically, such hemorrhages lead to severe headaches, focal neurological deficits, and epileptic seizures. CCM is caused by loss of function mutations in one of the three well-known CCM genes: Krev interaction trapped 1 (KRIT1), OSM, and programmed cell death 10 (PDCD10). Loss of CCM genes have been shown to be synergistically related to decreased Notch signaling and excessive angiogenesis. Despite recent evidences indicating that Notch signaling plays a pivotal role in regulating angiogenesis, the role of Notch in CCM development and progression is still not clear. Here, we provide an update literature review on the current knowledge of the structure of Notch receptor and its ligands, its relevance to angiogenesis and more precisely to CCM pathogenesis. In addition to reviewing the current literatures, this review will also focus on the cross talk between Delta-Notch and vascular endothelial growth factor (VEGF) signaling in angiogenesis and in CCM pathogenesis. Understanding the role of Notch signaling in CCM development and progression might help provide a better insight for novel anti-angiogenic therapies.
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PMID:Role of Delta-Notch signaling in cerebral cavernous malformations. 2677 17