|
rs28934906
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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
|
|
|
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 |