|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
RTT females with the T158M missense mutation are often atypical with mainly behavioral characteristics in infancy and childhood but become classic RTT in adolescence after a slower, protracted course.
|
19133691 |
2009 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
In the cohort of Angelman-negative patients (N=63), two missense mutations (p.R133C in a female patient and a mosaic p.T158M in a male patient) were found, which have been reported many times in patients with classical RTT syndrome.
|
14560307 |
2004 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
Consistent with reduced neuronal growth and complexity in Rett syndrome (RTT) brains, overexpression of human MECP2 carrying missense mutations common in RTT individuals (R106W or T158M) reduced dendritic and axonal length.
|
19217433 |
2009 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
One of the most common MeCP2 mutations associated with RTT occurs at threonine 158, converting it to methionine (T158M) or alanine (T158A).
|
22119903 |
2011 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
To facilitate the study of cellular mechanisms in human cells, we established several human stem cell lines: human embryonic stem cell (hESC) line carrying the common T158M mutation (<i>MECP2<sup>T158M/T158M</sup></i> ), hESC line expressing no MECP2 (<i>MECP2-KO</i>), congenic pair of wild-type and mutant RTT patient-specific induced pluripotent stem cell (iPSC) line carrying the V247fs mutation (V247fs-WT and V247fs-MT), and iPSC line in which the V247fs mutation was corrected by CRISPR/Cas9-based genome editing (V247fs-MT-correction).
|
28270572 |
2017 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
In classic RTT, poor growth was associated with worse development, higher disease severity, and certain MECP2 mutations (pre-C-terminal truncation, large deletion, T158M, R168X, R255X, and R270X).
|
23035069 |
2012 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
Together, these findings demonstrate that increasing MeCP2 T158M protein expression is sufficient to mitigate RTT-like phenotypes and support the targeting of MeCP2 T158M expression or stability as an alternative therapeutic approach.
|
28394263 |
2017 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice.
|
26647311 |
2016 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT.
|
15737703 |
2005 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
Lower doses of this vector significantly extended the survival of mice lacking MeCP2 or expressing a mutant T158M allele but had no impact on RTT-like neurological phenotypes.
|
28497075 |
2017 |
|
rs28934906
|
|
Rett Syndrome
|
|
0.900 |
GeneticVariation
|
BEFREE |
Combining this approach with an allelic series of knock-in mice carrying frequent RTT-associated mutations (encoding T158M and R106W) enabled the selective profiling of RTT-associated nuclear transcriptomes in excitatory and inhibitory cortical neurons.
|
28920956 |
2017 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Mutation screening in Rett syndrome patients.
|
10745042 |
2000 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Molecular diagnostic dilemmas in Rett syndrome.
|
22277191 |
2012 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Consistent with reduced neuronal growth and complexity in Rett syndrome (RTT) brains, overexpression of human MECP2 carrying missense mutations common in RTT individuals (R106W or T158M) reduced dendritic and axonal length.
|
19217433 |
2009 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Although more than 200 different MECP2 mutations have been identified throughout the gene, 7 of those (p.R133C, p.T158M, p.R168X, p.R255X, p.R270X, p.R294X, and p.R306C) account for up to two-thirds of pathogenic mutations in RTT patients.
|
19309269 |
2009 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Mutation analysis of the MECP2 gene in patients with Rett syndrome.
|
12567420 |
2003 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Mutations in the MECP2 gene in a cohort of girls with Rett syndrome.
|
10991689 |
2000 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update.
|
16473305 |
2006 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Functional consequences of Rett syndrome mutations on human MeCP2.
|
11058114 |
2000 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
GeneticVariation
|
CLINVAR |
MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome.
|
17089071 |
2007 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Rett syndrome: North American database.
|
18174548 |
2007 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Diagnostic testing for Rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene: identification of several novel mutations and polymorphisms.
|
11055898 |
2000 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Spectrum and distribution of MECP2 mutations in 64 Italian Rett syndrome girls: tentative genotype/phenotype correlation.
|
11738883 |
2001 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
CausalMutation
|
CLINVAR |
Mutational analysis of the MECP2 gene in Tunisian patients with Rett syndrome: a novel double mutation.
|
20631224 |
2010 |
|
rs28934906
|
|
Rett Syndrome
|
A |
0.900 |
GeneticVariation
|
CLINVAR |
Homozygosity for MECP2 gene in a girl with classical Rett syndrome.
|
17881312 |
2008 |