Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we report the case of a patient displaying an abnormal chromatin clumping (ACC) syndrome, a rare disease which shares features with both myeloproliferative and myelodysplastic disorders. Although various non specific cytogenetic abnormalities have been observed in ACC, the presence of a Ph1 chromosome has not been reported. In our patient, despite a lack of Ph1, PCR analysis of blood and bone marrow samples revealed a BCR-ABL rearrangement. These results indicate that at least some cases of ACC syndrome could represent a form of Ph1-negative chronic myeloid leukaemia.
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PMID:Abnormal chromatin clumping in granulocytes in a case of Ph1-negative, BCR-ABL rearrangement positive, haematologically atypical chronic myeloid leukaemia (CML). 890 5

Cowden disease, also known as multiple hamartoma syndrome, is a rare disease inherited in an autosomal dominant pattern, which confers a high risk of developing breast and thyroid carcinomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with Cowden disease. In this work, the direct sequencing of all coding regions of the PTEN gene led us to the identification of N48K, a new germline PTEN missense mutation, in a patient suffering from Cowden disease. The genetic analysis of 200 chromosomes from healthy individuals revealed that the variant was not common in our population. Moreover, by functional analysis we found that the ability of PTEN N48K mutant protein to inhibit the activation of the proto-oncogene PKB/Akt was impaired, supporting the involvement of N48K mutation in Cowden disease. Loss of heterozygosity using three microsatellites (D10S215, D10S541, and D10S564) and the complete sequence analysis of PTEN exons in breast and endometrial tumor samples from the same patient were also carried out in an attempt to identify additional PTEN somatic mutations. The lack of loss of heterozygosity or additional mutations in tumor samples suggests that abnormalities of the regulatory regions of the PTEN gene or haplo-insufficiency might occur in tumors from Cowden disease patients.
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PMID:A novel loss-of-function mutation (N48K) in the PTEN gene in a Spanish patient with Cowden disease. 1467 82

Philadelphia (Ph) chromosome-positive acute myelogenous leukemia (AML) is a rare disease that is resistant to conventional antitumor chemotherapy and has a poor prognosis. We describe a case of Ph chromosome-positive AML in which imatinib mesylate was used and a favorable outcome was obtained.A 64-year-old man was found to have Ph chromosome-positive, minor BCR-ABL-positive AML. Remission could not be induced by remission induction therapy with antitumor agents. Because the patient had a serious concomitant infectious disease, administration of 600 mg/day of imatinib mesylate, a specific inhibitor of BCR-ABL tyrosine kinase, was started after written informed consent was obtained. Complete cytogenetic response (CCR) was achieved without serious adverse events and persisted for more than 1 year. Our results suggested that imatinib mesylate was very useful for treating Ph chromosome-positive AML.
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PMID:Successful treatment with imatinib mesylate in a case of minor BCR-ABL-positive acute myelogenous leukemia. 1581 35

Chronic neutrophilic leukemia (CNL) is a rare disease and can cause considerable diagnostic difficulty. Although the V617F JAK2 mutation has been described by several groups to be associated with classical myeloproliferative disorders (MPD), this same mutation has been detected with a low incidence in atypical MPD, such as CNL. Here we report the presence of the V617F mutation in a CNL patient, who is unusual for having survived for more than 96 months, with little disease progression. It remains to be established what role this mutation, which gives cells a proliferative advantage, might play in the pathogenesis and prognosis of rare atypical MPD.
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PMID:Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinase mutation. 1633 Apr 46

We report the case of a 72-year-old man who had the very rare disease acute basophilic leukemia with the sole chromosomal finding of a monosomy 7. Most nuclear cells in the peripheral blood and bone marrow samples were either basophils or blasts. The blasts showed negative reaction with myeloperoxidase, periodic acid Schiff, chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, and Sudan black B. Metachromatic features of the blasts, however, were observed with toluidine blue stain. Electron microscopic evaluation showed the typical ultrastructure, with basophil and immature mast cell granules. Cytogenetic study revealed monosomy 7 in all metaphase cells, and this finding was confirmed by fluorescence in situ hybridization. The Philadelphia chromosome was absent. Review of the literature revealed abnormalities in cases of ABL. To our knowledge, the case reported here is the first to have basophilic leukemia with monosomy 7 as the only chromosome abnormality.
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PMID:Monosomy 7 as the sole abnormality of an acute basophilic leukemia. 1721 28

Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3 cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer (PIT) membrane-associated protein (PITPNM3) (MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B (rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram (ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.
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PMID:Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families. 1737 20

Lymphogranuloma venereum in the United Kingdom was detected in 2004, following the introduction of enhanced surveillance. This report describes a previously undiagnosed case, detected retrospectively in a sample obtained in 2003 from a male patient with high-risk behaviour, indicating that this previously rare disease in Europe, was present in the UK in 2003.
Int J STD AIDS 2008 Feb
PMID:Lymphogranuloma venereum in the UK in 2003. 1859 88

Malignant syphilis is now considered a rare disease, more commonly affecting individuals with poor health, malnutrition or HIV infection. We present a 34-year-old man with HIV infection who developed multiple atypical cutaneous ulcerations, leonine facies, a scleral nodule and keratitis with visual loss. The diagnosis of malignant syphilis was delayed due to the insidious presentation, but was confirmed via immunohistochemical (IHC) staining with anti-Treponema antibodies of a skin biopsy. Significant clinical improvement was observed following a 15-day course of penicillin and tigecycline therapy. In advanced HIV disease, cutaneous manifestations are often difficult to identify and present a challenge for the clinician. Clinical manifestations of secondary syphilis vary greatly, earning the epigram of 'the great imitator'. It is important to recognize atypical presentations of syphilis, especially among HIV-infected individuals. Unlike historical cases of malignant syphilis, Treponema pallidum was found in the tissue section using IHC staining methods. We emphasize the importance of lues maligna in the differential diagnosis of HIV-infected patients with diffuse ulceronodular lesions as well as the usefulness of histological investigations and IHC studies.
Int J STD AIDS 2011 May
PMID:Malignant syphilis with ocular involvement in an HIV-infected patient. 2157 84

"Refractory anemia with ring sideroblasts and thrombocytosis" (RARS-T) is a rare disease, a provisional entity, with a controversial status in the 2008 revised WHO classification. Even at present time, RARS-T is a matter of debate whether it is a distinct clinicopathological entity or more likely a constellation of clinical and pathological features of two well-defined myeloid neoplasms, myelodysplastic syndrome and myeloproliferative neoplasm. Perhaps none of the clonal disorders illustrates better the challenges presented by the current classification of myeloid neoplasms, than this clinical entity with overlapping features of both refractory anemia with ring sideroblasts and essential thrombocythemia. The purpose of this study is to present the evolution of such a case, with difficulties in establishing not only the correct diagnosis, but also the appropriate therapeutic approach. For this reported case, we present documented details regarding persistent thrombocytosis, slightly increased number of leukocytes and analysis of Janus kinase 2 (JAK2) genes that revealed a V617F mutation, confirming the presence of an underlying myeloproliferative neoplasm, followed later in the evolution by occurrence of myelodysplastic features as ring sideroblasts. This case might interest pathologists, but especially clinicians, for at least two reasons: the rarity of this disease and the lack of data on prognosis of these patients, probably because of relatively recent established diagnosis criteria and existence of few studies with small number of patients. The third interesting aspect for practitioners would be the absence of consensus on optimal clinical treatment for this disorder, because there are few cases that meet the rigorous diagnostic criteria.
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PMID:Refractory anemia with ring sideroblasts associated with marked thrombocytosis: case report and literature review. 2299 May 61

Spondyloarthritis (SpA) represents a group of inflammatory rheumatic diseases that cluster within families and possess overlapping clinical features. The pathogenesis of SpA encompasses a complex array of genetic, immunological and environmental factors. In this article, we will briefly review the genetics of PsA, and then focus on the genes that may be potentially linked either directly or indirectly to the immunopathology of the Th-17 pathway. The most consistent and dominant genetic effect of PsV and PsA is located on chromosome 6p21.3 within the major histocompatibility complex (MHC) region, which accounts for approximately one-third of the genetic contribution of PsV and PsA. To date, 36 genes have reached genome-wide significance, accounting for approximately 22% of psoriasis (PsV) heritability. Prominent genes identified via GWAS include HLA-Cw6, IL12B, IL23R, IL23A, TNIP1, TNFAIP3, LCE3B-LCE3C, TRAF3IP2, NFkBIA, FBXL19, TYK2, IFIH1, REL, and ERAP1. Genes identified in psoriatic arthritis (PsA) has largely echoed those in PsV and include HLA-B/C, HLA-B, IL-12B, IL-23R, TNIP1, TRAF3IP2, FBXL19, and REL. The lack of identified genetic susceptibility loci is largely attributed to the much smaller number of PsA patients and the greater clinical heterogeneity of PsA. Searching for different types of genetic variants such as small CNVs and/or insertions/deletions has also led to the identification of several genes with a function relative to PsV in particular including DEFB4, LCE3C_LCE3B, and IL-22 gene (exon 1). The candidate genes identified in PsV/PsA have highlighted pathways of critical importance to psoriatic disease including distinct signaling pathways comprised of barrier integrity, innate immune response and adaptive immune response, mediated primarily by Th-17 and Th-1 signalling. While GWAS studies have yielded great insights into the genes that contribute to the pathogenesis of PsV and PsA, replication in large cohorts, fine-mapping and resequencing efforts, together with functional studies of genetic variants identified, are warranted to better understand susceptibility to and progression of these diseases. That searching solely for common variants by GWAS will identify only a fraction of the entire genetic burden of disease, a concerted effort is underway to search for highly penetrant but rare disease alleles in families with PsV and PsA, using next-generation sequencing and through epigenetic investigations.
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PMID:Genetics of psoriatic arthritis. 2548 77


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