Search results for "mutation."
showing 10 items of 2808 documents
Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.
2019
Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…
Development of systemic lupus erythematosus in a patient with selective complete C1q deficiency
1997
A 7-year-old male with recurrent erythematous and desquamated skin lesions and respiratory infections was diagnosed as selective complete C1q deficiency following detailed studies of the complement system. His asymptomatic sister also had selective complete C1q deficiency. During a follow up period of 3 years, his skin lesions persisted, he suffered from recurrent bronchopneumonias and glomerulonephritis developed. Renal function deteriorated with the appearance of anti-DNA antibodies. Renal biopsy was consistent with systemic lupus erythematosus. The patient was treated with immunosuppressive drugs, but died of renal failure. It is postulated that in this patient defective clearance of ant…
Boy with pseudohypoparathyroidism type 1a caused byGNASgene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding
2009
We report on a 6-month-old boy with craniosynostosis, pseudohypoparathyroidism type 1a (PHP1A), and a GNAS gene mutation. He had synostoses of the coronal, frontal, and sagittal sutures, brachyturricephaly, and hydrocephaly. He also had congenital hypothyroidism, round face, full cheeks, shortness of limbs, mild developmental delay, and muscular hypotonia. Because of progressive hydrocephaly, the synostosis was corrected surgically but circulatory decompensation led to disseminated intravascular coagulation and cerebral infarctions. Our patient died 8 days later. Postmortem molecular studies of GNAS, the gene for guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (ge…
Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in a Mediterranean area.
2001
Abstract Background. Thromboembolism has been reported to be associated with inflammatory bowel disease. Aim. To evaluate the association of factor V Leiden and prothrombin gene mutation with inflammatory bowel disease in a population of patients with thromboembolic events and inflammatory bowel disease and in a control population of patients with inflammatory bowel disease without thromboembolic events. Patients and methods. A series of 18 patients with inflammatory bowel disease and a history of arterial or venous thrombosis and 45 patients with inflammatory bowel disease without thromboembolic events were evaluated for the presence of factor V Leiden and prothrombin gene mutation. Freque…
A premature infant with Costello syndrome due to a rare G13C HRAS mutation.
2009
Costello syndrome is caused by mutations in the HRAS proto-oncogene whose clinical features in the first year of life include fetal and neonatal macrosomia with subsequent growth impairment due to severe feeding difficulties. We report on a premature male with Costello syndrome due to a rare G13C HRAS mutation and describe his clinical features and evolution during the first year of life. The diagnosis of Costello syndrome may be difficult at birth, especially in very preterm infants in whom feeding difficulties, reduced subcutaneous adipose tissue and failure to thrive are also part of their typical presentation.
Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy.
2014
Background There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. Methodology Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), non-classifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients’ general practitioners. Results Out of the …
Hyperekplexia caused by dominant-negative suppression of glyra1 function.
2007
Hyperekplexia (HE; startle disease; OMIM#149400) is a rare inheritable neurologic disorder characterized by an exaggerated response to sudden stimuli, muscular rigidity, and hyperreflexia, leading to chronic injuries due to unprotected falls. All symptoms are present at birth but gradually decline during the first year of life, although an exaggerated startle response remains during adulthood.1 Dysfunctional inhibitory neurotransmission by glycine (Gly) plays a central role in HE pathogenesis. All patients with HE carry mutations in genes encoding either for α1 (GLYRA1) or β (GLYRB) Gly receptor subunits, presynaptic Gly transporters (SLC6A5), or proteins involved in Gly receptor (GLYR) clu…
Janus kinase (JAK) 2 V617F mutation as the cause of primary thrombocythemia in acromegaly with severe visceromegaly and divergence between growth hor…
2012
OBJECTIVE: An increased prevalence of hematological abnormalities is reported in acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2 mutation in acromegalic patients have been described. DESIGN: We report the complex clinical presentation of the unique case, never described, of acromegaly due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation. RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2 V617F mutation, severe visceromegaly and a peculiar clinical course of the disease characterized by discrepant values of GH and IGF-1 during somatostatin analog (SA) treatment despite a significant reduction in pituitary a…
Association of cathepsin B gene polymorphisms with tropical calcific pancreatitis
2006
Background and aims: Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to countries in the tropics. Mutations in pancreatic secretory trypsin inhibitor (SPINK1) rather than cationic trypsinogen (PRSS1) explain the disease in only 50% of TCP patients. As cathepsin B (CTSB) is known to activate cationic trypsinogen, we attempted to understand the role of CTSB mutations in TCP. Evidence of epistatic interaction was investigated with the previously associated N34S SPINK1 allele, a variant considered to be a modifier rather than a true susceptibility allele. Subjects and methods: We sequenced the coding region of CTSB gene in 51 TCP patients and 25 controls and furthe…
Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations
2004
Contains fulltext : 48815.pdf (Publisher’s version ) (Closed access) Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus, developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein. In this study, phenotypic manifestations of patients with and without MID1 mutations were compared to determine genotype-phenotype correlations. We detected 10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families for whom it …