scholarly journals X‐linked hypohidrotic ectodermal dysplasia: clinical and molecular genetic analysis of a large Russian family with a synonymous p.Ser267= (c.801A>G) splice site mutation

2019 ◽  
Vol 33 (12) ◽  
Author(s):  
T.B. Milovidova ◽  
O.A. Schagina ◽  
M.V. Freire ◽  
N.A. Demina ◽  
A.Y. Filatova ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Splice Site ◽  
Ectodermal Dysplasia ◽  
Molecular Genetic ◽  
Splice Site Mutation ◽  
Molecular Genetic Analysis ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Site Mutation

A rare cause of fever of unknown origin: hypohidrotic ectodermal dysplasia with a splice site mutation

2018 ◽  
Vol 70 (5) ◽  
Author(s):  
Melahat M. Oguz ◽  
Meltem Akcaboy ◽  
Asuman Gurkan ◽  
Esma Altinel Acoglu ◽  
Pelin Zorlu ◽  
...  
Keyword(s):  
Splice Site ◽  
Fever Of Unknown Origin ◽  
Ectodermal Dysplasia ◽  
Splice Site Mutation ◽  
Unknown Origin ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Site Mutation

scholarly journals Molecular Genetic Analysis of Revertants from a Poliovirus Mutant That Is Specifically Adapted to the Mouse Spinal Cord

2001 ◽  
Vol 75 (23) ◽  
pp. 11766-11772 ◽  
Author(s):  
Qingmei Jia ◽  
James M. Hogle ◽  
Tsutomu Hashikawa ◽  
Akio Nomoto
Keyword(s):  
Amino Acid ◽  
Genetic Analysis ◽  
Single Point ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Amino Acid Residues ◽  
Site Mutation ◽  
Mutation Site ◽  
Large Plaque ◽  
Inoculation Route

ABSTRACT SA virus, a mutant of the Mahoney strain of type 1 poliovirus (PV1/Mahoney), replicates specifically in the spinal cords of mice and causes paralysis, although the PV1/Mahoney strain does not show any mouse neurovirulence (Q. Jia, S. Ohka, K. Iwasaki, K. Tohyama, and A. Nomoto, J. Virol. 73:6041–6047, 1999). The key mutation site for the mouse neurovirulence of SA was mapped to nucleotide (nt) 928 of the genome (A to G), resulting in the amino acid substitution of Met for Ile at residue 62 within the capsid protein VP4 (VP4062). A small-plaque phenotype of SA appears to be indicative of its mouse-neurovirulent phenotype. To identify additional amino acid residues involved in the host range determination of PV, a total of 14 large-plaque (LP) variants were isolated from a single point mutant, Mah/I4062M, that showed the SA phenotype. All the LP variants no longer showed any mouse neurovirulence when delivered via an intraspinal inoculation route. Of these, 11 isolates had a back mutation at nt 928 (G to A) that restored the nucleotide of the PV1/Mahoney type. The reversions of the remaining three isolates (LP8, LP9, and LP14) were mediated by a second site mutation. Molecular genetic analysis involving recombinants between Mah/I4062M and the LP variants revealed that the mere substitution of an amino acid residue at position 107 in VP1 (Val to Leu) (LP9), position 33 in VP2 (Val to Ile) (LP14), or position 231 in VP3 (Ile to Thr) (LP8) was sufficient to restore the PV1/Mahoney phenotype. These amino acid residues are located either on the surface or inside of the virus particle. Our results indicate that the mouse neurovirulence of PV is determined by the virion surface structure, which is formed by all four capsid proteins.

Decreased Expression In NF-κB Essential Modulator Due to a Novel Splice-Site Mutation Causes Ectodermal Dysplasia with Immunodeficiency

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1732-1732
Author(s):  
Shuhei Karakawa ◽  
Satoshi Okada ◽  
Miyuki Tsumura ◽  
Yoko Mizoguchi ◽  
Norioki Ohno ◽  
...  
Keyword(s):  
Splice Site ◽  
Transcriptional Activity ◽  
Ectodermal Dysplasia ◽  
Splice Site Mutation ◽  
The Other ◽  
Dominant Negative Effect ◽  
Site Mutation ◽  
Streptococcus Pneumonia ◽  
Cell Counts ◽  
Ifn Γ

Abstract Abstract 1732 <Introduction> X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the nuclear factor κB (NF-κB) essential modulator (NEMO) gene, also called IKBKG, and these mutations impair but do not abolish NF-κB signaling, resulting in distinct clinical and immunologic phenotypes. We presented the patient with XL-EDA-ID showing a novel splice-site mutation. In this report we precisely study the involvement of this mutation in the molecular pathogenesis of XL-EDA-ID. <Patient> The patient is 12 years old Japanese boy. He had conical-shaped teeth and hypodontia. He had suffered from recurrent bacterial infections and these pathogenic bacteria were mostly streptococcus pneumonia. The laboratory examination revealed that the number of white blood cell counts, the classification of lymphocytes, and the serum immunoglobulin levels were within normal range. However the specific antibodies against measles and streptococcus pneumonia were negative in spite of these infections. <Results> We identified a novel hemizygous mutation, 769-1 G>C, at the splicing acceptor site of exon 7 in the IKBKG gene. In order to clarify the effect of this mutation on mRNA, we performed a cloning analysis. Although various abnormal spliced NEMO (mutant NEMO) mRNAs were observed, a small amount of wild-type NEMO (WT NEMO) mRNA was also identified. The rate of WT and mutant was variable on the time of blood collection. Further we performed FACS and immunoblot analysis in order to evaluate the effect of this mutation at protein level. Two major bands which were presumed to be derived from WT and one mutant were detected in immunoblots using EBV transfected B cells, however the expression levels of these bands were markedly decreased compared to those of the healthy controls. The NEMO protein expression was confirmed to be decreased in various lineages of leukocytes. We generated WT and two representative mutant NEMO constructs and measured their NF-κB transcriptional activity using reporter assay. One mutant NEMO abolished NF-κB transcriptional activity, the other showed weak activity. However, neither of mutant NENO showed a dominant-negative effect against WT NEMO activity. CD14+ cells from the patient produced a lower level of TNF-α in response to IFN-γ stimulation, on the other hand CD3+ cells produced very little IFN-γ in response to IL-12. CD4+ T-cell proliferation was impaired in response to measles and mumps, but not rubella. <Conclusion> The hemizygous 769-1 G>C mutation was shown to cause the decreased expression of WT NEMO protein, resulting in the decrease in NF-κB activation and the development of XL-EDA-ID. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique splice site mutation in TCIRG1 gene spread by the founder effect

2009 ◽  
Vol 17 (5) ◽  
pp. 664-672 ◽  
Author(s):  
Elena A Bliznetz ◽  
Svetlana M Tverskaya ◽  
Rena A Zinchenko ◽  
Anna V Abrukova ◽  
Ekaterina N Savaskina ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Autosomal Recessive Osteopetrosis
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