Spectrum of mutations in the arylsulfatase A gene in a Canadian DNA collection including two novel frameshift mutations, a new missense mutation (C488R) and an MLD mutation (R84Q) in cis with a pseudodeficiency allele

2003 ◽  
Vol 79 (2) ◽  
pp. 91-98 ◽  
Author(s):  
M Coulter-Mackie
Keyword(s):  
Missense Mutation ◽  
Arylsulfatase A ◽  
Frameshift Mutations ◽  
Dna Collection ◽  
In Cis ◽  
Pseudodeficiency Allele

Ty1 in vitro integration: effects of mutations in cis and in trans

1994 ◽  
Vol 14 (9) ◽  
pp. 5731-5740
Author(s):  
L T Braiterman ◽  
J D Boeke
Keyword(s):  
Missense Mutation ◽  
Frameshift Mutations ◽  
Amino Terminal ◽  
Dna Molecule ◽  
Conserved Domain ◽  
In Trans ◽  
In Cis ◽  
Obvious Similarity ◽  
Insertion Mutations

Mutations within the TYB gene of Ty1 encoding integrase (IN) as well as alterations in its substrate, a linear DNA molecule, were examined for their effects on in vitro IN activity, using a recently developed physical assay. Five different codon-insertion mutations, two frameshift mutations, and one missense mutation, previously identified as transposition-deficient mutations, were tested. Virus-like particles, the source of IN, from two different protease mutants and a reverse transcriptase mutant exhibited near-normal to normal IN activity. Two frameshift mutations mapping within the phylogenetically variable C-terminal domain of IN resulted in significant in vitro IN activity. In contrast, three mutations within the amino-terminal conserved domain of IN completely abolished IN activity. When the substrate termini were mutated, we found that substrates with as few as 4 bp of Ty1 termini were capable of efficiently generating integration products. Surprisingly, certain substrates that lacked obvious similarity to Ty1 termini were also readily integrated into both linear and circular targets, whereas others were not used as substrates at all. Termini rich in adenosine residues were among the more active substrates; however, certain substrates lacking terminal adenosine residues can form small quantities of integration products, including complete integration reactions.

scholarly journals Ty1 in vitro integration: effects of mutations in cis and in trans.

1994 ◽  
Vol 14 (9) ◽  
pp. 5731-5740 ◽  
Author(s):  
L T Braiterman ◽  
J D Boeke
Keyword(s):  
Missense Mutation ◽  
Frameshift Mutations ◽  
Amino Terminal ◽  
Dna Molecule ◽  
Conserved Domain ◽  
In Trans ◽  
In Cis ◽  
Obvious Similarity ◽  
Insertion Mutations

Mutations within the TYB gene of Ty1 encoding integrase (IN) as well as alterations in its substrate, a linear DNA molecule, were examined for their effects on in vitro IN activity, using a recently developed physical assay. Five different codon-insertion mutations, two frameshift mutations, and one missense mutation, previously identified as transposition-deficient mutations, were tested. Virus-like particles, the source of IN, from two different protease mutants and a reverse transcriptase mutant exhibited near-normal to normal IN activity. Two frameshift mutations mapping within the phylogenetically variable C-terminal domain of IN resulted in significant in vitro IN activity. In contrast, three mutations within the amino-terminal conserved domain of IN completely abolished IN activity. When the substrate termini were mutated, we found that substrates with as few as 4 bp of Ty1 termini were capable of efficiently generating integration products. Surprisingly, certain substrates that lacked obvious similarity to Ty1 termini were also readily integrated into both linear and circular targets, whereas others were not used as substrates at all. Termini rich in adenosine residues were among the more active substrates; however, certain substrates lacking terminal adenosine residues can form small quantities of integration products, including complete integration reactions.

An arylsulfatase A (ARSA) missense mutation (T274M) causing late-infantile metachromatic leukodystrophy

1993 ◽  
Vol 2 (4) ◽  
pp. 261-267 ◽  
Author(s):  
John S. Harvey ◽  
Paul V. Nelson ◽  
William F. Carey ◽  
Evelyn F. Robertson ◽  
C. Phillip Morris
Keyword(s):  
Missense Mutation ◽  
Metachromatic Leukodystrophy ◽  
Arylsulfatase A

scholarly journals Frameshift mutations in the v-src gene of avian sarcoma virus act in cis to specifically reduce v-src mRNA levels.

1994 ◽  
Vol 14 (3) ◽  
pp. 1835-1844 ◽  
Author(s):  
S B Simpson ◽  
C M Stoltzfus
Keyword(s):  
Chicken Embryo Fibroblast ◽  
Cdna Clones ◽  
Mrna Levels ◽  
Avian Sarcoma Virus ◽  
Frameshift Mutations ◽  
Src Gene ◽  
Sarcoma Virus ◽  
In Trans ◽  
In Cis ◽  
Avian Sarcoma

A portion of the avian sarcoma virus (ASV) primary RNA transcripts is alternatively spliced in chicken embryo fibroblast cells to two different messages, the src and env mRNAs. Frameshift mutations of the viral genome causing premature translation termination within the src gene result in a decreased steady-state level of the src mRNA. In marked contrast, frameshift mutations at various positions of the env gene do not decrease the level of the env mRNA. We show that the src gene product is not required in trans for splicing and accumulation of src mRNA. Conversely, the truncated Src proteins do not act negatively in trans to decrease specifically the levels of src mRNA. Taken together, these results indicate that the frameshift mutations act in cis to reduce src mRNA levels. A double mutant with a lesion in the src initiator AUG and a frameshift within the src gene demonstrated wild-type RNA levels, indicating that the src mRNA must be recognized as a translatable mRNA for the effect on src mRNA levels to occur. Our results indicate that the reduced levels do not result from decreased cytoplasmic stability of the mature src mRNA. We also show that the src gene frameshift mutations affect src mRNA levels when expressed from intronless src cDNA clones. We conclude that the reduction of src mRNA levels triggered by the presence of frameshift mutations within the src gene occurs while it is associated with the nucleus. Our data also strongly suggest that this occurs at a step of RNA processing or transport independent of RNA splicing.

Clinical, Molecular, and Computational Analysis in Patients With a Novel Double Mutation and a New Synonymous Variant in MeCP2: Report of the First Missense Mutation Within the AT-hook1 Cluster in Rett Syndrome

2017 ◽  
Vol 32 (8) ◽  
pp. 694-703 ◽  
Author(s):  
Marwa Kharrat ◽  
Yosra Kamoun ◽  
Fatma Kamoun ◽  
Emna Ellouze ◽  
Marwa Maalej ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Rett Syndrome ◽  
Phenotypic Variability ◽  
Neurodevelopmental Disorder ◽  
Clinical Severity ◽  
Bioinformatics Analyses ◽  
Double Mutation ◽  
Synonymous Variant ◽  
In Cis ◽  
The Relationship

Rett syndrome is an X-linked neurodevelopmental disorder, primarily caused by MECP2 mutations. In this study, clinical, molecular and bioinformatics analyses were performed in Rett patients to understand the relationship between MECP2 mutation type and the clinical severity. Two double MeCP2 mutations were detected: a novel one (p.G185 V in cis with p.R255X) in P1 and a known one (p.P179 S in cis with p.R255X) in P2. Besides, a novel synonymous mutation (c.807C>T; p.G269G), which could affect mRNA splicing, was identified in P3. The results from clinical severity analysis have shown that P1 was more severely affected than P2 with CSS being 35 and 14, respectively. Therefore, the phenotypic variability in P1 and P2 could be explained by the potential pathogenic effect of the RTT-causing missense mutation p.G185 V in the AT-hook1. In conclusion, clinical, molecular, and in silico investigations in the studied patients have been proven to be substantial for the genotype-phenotype correlation.

scholarly journals A synonymous RET substitution enhances the oncogenic effect of an in-cis missense mutation by increasing constitutive splicing efficiency

PLoS Genetics ◽  
2018 ◽  
Vol 14 (10) ◽  
pp. e1007678 ◽  
Author(s):  
Valeria Pecce ◽  
Marialuisa Sponziello ◽  
Giuseppe Damante ◽  
Francesca Rosignolo ◽  
Cosimo Durante ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Constitutive Splicing ◽  
Splicing Efficiency ◽  
In Cis

Prevalence of Arylsulfatase A Pseudodeficiency Allele in Metachromatic Leukodystrophy Patients from Poland

2000 ◽  
Vol 44 (2) ◽  
pp. 104-107 ◽  
Author(s):  
Agnieszka Ługowska ◽  
Barbara Czartoryska ◽  
Anna Tylki-Szymańska ◽  
Mariola Bisko ◽  
Janusz G. Zimowski ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Arylsulfatase A ◽  
Pseudodeficiency Allele
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