scholarly journals Functional Analysis of the C.3705+5G>C Mutation in the SCN1A Gene: Cryptic Splicing Site Activation and Partial Exon Skipping

2016 ◽  
Vol 10 (4) ◽  
Author(s):  
Mahmoud AB ◽  
Fakhfakh F ◽  
Mansour RB ◽  
Driss F
Keyword(s):  
Functional Analysis ◽  
Exon Skipping ◽  
Scn1a Gene ◽  
Splicing Site

scholarly journals Identification of eight exonic variants in the SLC4A1, ATP6V1B1 and ATP6V0A4 gene that alter RNA splicing by minigene assay

2021 ◽  
Author(s):  
Ruixiao Zhang ◽  
Zeqing Chen ◽  
Qijing Song ◽  
Sai Wang ◽  
Zhiying Liu ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Mrna Level ◽  
Exon Skipping ◽  
Regulatory Elements ◽  
Mrna Splicing ◽  
Splicing Regulatory Elements ◽  
Renal Tubular ◽  
Splicing Site ◽  
Minigene Assay

Primary distal renal tubular acidosis (dRTA) is a rare tubular disease associated with variants in SLC4A1, ATP6V0A4, ATP6V1B1, FOXⅠ1 or WDR72 genes. Currently, there is growing evidence that all types of exonic variants can alter splicing regulatory elements, affecting the pre-mRNA splicing process. This study was to determine the consequences of variants associated with dRTA on pre-mRNA splicing combined with predictive bioinformatics tools and minigene assay. As a result, among the 15 candidate variants, 8 variants distributed in SLC4A1 (c.1765C>T, p.Arg589Cys), ATP6V1B1( c.368G>T, p.Gly123Val; c.370C>T, p.Arg124Trp; c.484G>T, p.Glu162* and c.1102G>A, p.Glu368Lys) and ATP6V0A4 genes (c.322C>T, p.Gln108*; c.1571C>T, p.Pro524Leu and c.1572G>A, p.Pro524Pro) were identified to result in whole or part of exon skipping by either disruption of ESEs and generation of ESSs, or interference with the recognition of the classic splicing site, or both. To our knowledge, this is the first study on pre-mRNA splicing of exonic variants in the dRTA-related genes. These results highlight the importance of assessing the effects of exonic variants at the mRNA level and suggest that minigene analysis is an effective tool for evaluating the effects of splicing on variants in vitro

scholarly journals Identification and Functional Analysis of Mutations in the Hypocretin (Orexin) Genes of Narcoleptic Canines

2001 ◽  
Vol 11 (4) ◽  
pp. 531-539
Author(s):  
Marcel Hungs ◽  
Jun Fan ◽  
Ling Lin ◽  
Xiaoyan Lin ◽  
Richard A. Maki ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Novel Mutation ◽  
Disease Onset ◽  
Exon Skipping ◽  
Single Amino Acid ◽  
Membrane Localization ◽  
Loss Of Function ◽  
Hek 293 ◽  
Sporadic Cases ◽  
Multiplex Families

Narcolepsy is a sleep disorder affecting animals and humans. Exon skipping mutations of the Hypocretin/Orexin-receptor-2 (Hcrtr2) gene were identified as the cause of narcolepsy in Dobermans and Labradors. Preprohypocretin (Hcrt) knockout mice have symptoms similar to human and canine narcolepsy. In this study, 11 sporadic cases of canine narcolepsy and two additional multiplex families were investigated for possible Hcrt andHcrtr2 mutations. Sporadic cases have been shown to have more variable disease onset, increased disease severity, and undetectable Hypocretin-1 levels in cerebrospinal fluid. The canine Hcrtlocus was isolated and characterized for this project. Only one novel mutation was identified in these two loci. This alteration results in a single amino acid substitution (E54K) in the N-terminal region of the Hcrtr2 receptor and autosomal recessive transmission in a Dachshund family. Functional analysis of previously-described exon-skipping mutations and of the E54K substitution were also performed using HEK-293 cell lines transfected with wild-type and mutated constructs. Results indicate a truncated Hcrtr2 protein, an absence of proper membrane localization, and undetectable binding and signal transduction for exon-skipping mutated constructs. In contrast, the E54K abnormality was associated with proper membrane localization, loss of ligand binding, and dramatically diminished calcium mobilization on activation of the receptor. These results are consistent with a loss of function for all three mutations. The absence of mutation in sporadic cases also indicates genetic heterogeneity in canine narcolepsy, as reported previously in humans.

Functional Analysis of 114 Exon-Internal AONs for Targeted DMD Exon Skipping: Indication for Steric Hindrance of SR Protein Binding Sites

2005 ◽  
Vol 15 (4) ◽  
pp. 284-197 ◽  
Author(s):  
Annemieke Aartsma-rus ◽  
Christa L. De winter ◽  
Anneke A.M. Janson ◽  
Wendy E. Kaman ◽  
Gert-jan B. Van ommen ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Protein Binding ◽  
Steric Hindrance ◽  
Binding Sites ◽  
Exon Skipping ◽  
Sr Protein ◽  
Protein Binding Sites

Case Formulation and Design of Behavioral Treatment Programs

2003 ◽  
Vol 19 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Stephen N. Haynes ◽  
Andrew E. Williams
Keyword(s):  
Functional Analysis ◽  
Behavior Problems ◽  
Behavioral Treatment ◽  
Clinical Case ◽  
Relative Magnitude ◽  
Mechanisms Of Action ◽  
Treatment Programs ◽  
Case Formulation ◽  
Functional Relations ◽  
Causal Variables

Summary: We review the rationale for behavioral clinical case formulations and emphasize the role of the functional analysis in the design of individualized treatments. Standardized treatments may not be optimally effective for clients who have multiple behavior problems. These problems can affect each other in complex ways and each behavior problem can be influenced by multiple, interacting causal variables. The mechanisms of action of standardized treatments may not always address the most important causal variables for a client's behavior problems. The functional analysis integrates judgments about the client's behavior problems, important causal variables, and functional relations among variables. The functional analysis aids treatment decisions by helping the clinician estimate the relative magnitude of effect of each causal variable on the client's behavior problems, so that the most effective treatments can be selected. The parameters of, and issues associated with, a functional analysis and Functional Analytic Clinical Case Models (FACCM) are illustrated with a clinical case. The task of selecting the best treatment for a client is complicated because treatments differ in their level of specificity and have unequally weighted mechanisms of action. Further, a treatment's mechanism of action is often unknown.

The Social Order Yields to Functional Analysis

1958 ◽  
Vol 3 (6) ◽  
pp. 158-160
Author(s):  
LAWRENCE SCHLESINGER
Keyword(s):  
Functional Analysis ◽  
Social Order ◽  
The Social

A Functional Analysis of Reinforcement Within a Social System

1973 ◽  
Author(s):  
Robert M. Leve ◽  
Lydia Burdick ◽  
Patricia Fontaine
Keyword(s):  
Functional Analysis ◽  
Social System
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