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Missense Polymorphism (missense + polymorphism)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Novel missense polymorphism in the regulator of G-protein signaling 10 gene: analysis of association with schizophrenia

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2004
AKITOYO HISHIMOTO md
ABSTRACT, Dysfunction of neuronal signal transduction via G-protein has previously been speculated to be involved in the pathophysiology of schizophrenia. Regulator of G-protein signaling (RGS) is a protein that acts as a GTPase-activator for G, protein. A total of 33 Japanese patients with schizophrenia were screened for mutations in the coding region of the RGS10 gene, and a novel missense polymorphism (Val38Met) in the RGS domain was detected. A case-control study did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the RGS10 gene is involved in biological vulnerability to schizophrenia. [source]

Serum biomarker for progranulin-associated frontotemporal lobar degeneration,

ANNALS OF NEUROLOGY, Issue 5 2009
Kristel Sleegers MD
Objective Mutations that lead to a loss of progranulin (PGRN) explain a considerable portion of the occurrence of frontotemporal lobar degeneration. We tested a biomarker allowing rapid detection of a loss of PGRN. Methods We used an enzyme-linked immunosorbent assay to measure in serum the PGRN protein levels of six affected and eight unaffected carriers from within an extended Belgian founder family segregating the null mutation IVS1+5G>C. Further, we measured serum PGRN levels in 2 patients with another null mutation (a Met1 and a frameshift mutation), in 4 patients carrying a predicted pathogenic missense mutation and in 5 patients carrying a benign missense polymorphism, in 9 unaffected noncarrier relatives, and in 22 community controls. Results Serum PGRN levels were reduced in both affected and unaffected null mutation carriers compared with noncarrier relatives (pexact < 0.0001), and allowed perfect discrimination between carriers and noncarriers (sensitivity: 1.0; 1 , specificity: 0.0). Serum PGRN levels in Cys139Arg and Arg564Cys mutation carriers were significantly lower than in controls, but greater than in null mutation carriers, fitting the hypothesis of partial loss of function caused by these missense mutations. As expected, levels for carriers of benign missense polymorphisms were not significantly different from controls. Interpretation Our results indicate that the serum PGRN level is a reliable biomarker for diagnosing and early detection of frontotemporal lobar degeneration caused by PGRN null mutations, and provided the first in vivo evidence that at least some missense mutations in PGRN may lead to a (partial) loss of PGRN. Ann Neurol 2009 [source]