|
rs179363900
|
|
|
0.710 |
GeneticVariation |
BEFREE |
We show that a gradient of impairment is present when the p.P152A mutation is compared with an allelic p.P152R mutation, which causes classic Rett syndrome and another Rett syndrome-causing mutation, such that protein-heterochromatin binding observed by immunofluorescence and immunoblotting is wild-type > P152A > P152R > T158 M, consistent with the severity of the observed phenotype.
|
18989701 |
2009 |
|
rs267608454
|
|
|
0.720 |
GeneticVariation |
BEFREE |
Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.
|
29428602 |
2018 |
|
rs267608454
|
|
|
0.720 |
GeneticVariation |
BEFREE |
Therefore, we decided to characterize a novel MeCP2 phospho-isoform (Tyr-120) whose relevance was suggested by a Rett syndrome patient carrying a Y120D substitution possibly mimicking a constitutively phosphorylated state.
|
25527496 |
2015 |
|
rs267608475
|
|
|
0.710 |
GeneticVariation |
BEFREE |
A single nucleotide deletion, at codon 137, that creates a L138X stop codon within the methyl-binding domain was found in an individual with features of RTT and incontinentia pigmenti.
|
10577905 |
1999 |
|
rs267608563
|
|
|
0.010 |
GeneticVariation |
BEFREE |
The results showed the presence of 3 de novo point mutations in the C-terminal region: 2 novel mutations: c.1065C>A (p.S355R) and c.1030C>G (p.R344G) in the 2 typical Rett syndrome girls, but also the c.996C>T (p.S332S) mutation first described in the atypical Rett syndrome patient.
|
21940684 |
2012 |
|
rs267608591
|
|
|
0.710 |
GeneticVariation |
BEFREE |
We hypothesize that the presence of this mutation c.1160C>T (P387L) in the homozygous form is responsible for the Rett syndrome-like phenotype seen in this patient.
|
26755454 |
2016 |
|
rs267608595
|
|
|
0.010 |
GeneticVariation |
BEFREE |
We hypothesize that the presence of this mutation c.1160C>T (P387L) in the homozygous form is responsible for the Rett syndrome-like phenotype seen in this patient.
|
26755454 |
2016 |
|
rs267608597
|
|
|
0.010 |
GeneticVariation |
BEFREE |
The first one, the double nucleotide substitution c.1162_1163delinsTA leading to a premature stop codon (p.Pro388X) was found in a female patient with random X-inactivation, presenting with borderline mental impairment without any features of Rett syndrome.
|
17383248 |
2007 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
Three of these mutations (R106W, R133C, and F155S) have their binding affinities for methylated DNA reduced more than 100-fold; this is consistent with the hypothesis that impaired selectivity for methylated DNA of mutant MeCP2 contributes to Rett syndrome.
|
10852707 |
2000 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
RTT females with the frequently recurrent R133C and R306C missense mutations and those with intragenic deletions in the C-terminus of MECP2 deserve more attention in larger studies as their development is different and milder in the long term.
|
19133691 |
2009 |
|
rs28934904
|
|
|
0.880 |
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 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV).
|
15737703 |
2005 |
|
rs28934904
|
|
|
0.880 |
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 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
A sister with R133C displayed classic RTT.
|
16122633 |
2005 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
Clinicians need to be alerted to the variable presentation of Rett syndrome including the milder phenotypes of cases with the p.R133C or p.R294X mutation.
|
20815036 |
2010 |
|
rs28934904
|
|
|
0.880 |
GeneticVariation |
BEFREE |
The results are in agreement with previous experimental studies and further provide atomic level understanding of the molecular origin of RTT associated with R133C variant.
|
26064184 |
2015 |
|
rs28934905
|
|
|
0.810 |
GeneticVariation |
BEFREE |
Three of these mutations (R106W, R133C, and F155S) have their binding affinities for methylated DNA reduced more than 100-fold; this is consistent with the hypothesis that impaired selectivity for methylated DNA of mutant MeCP2 contributes to Rett syndrome.
|
10852707 |
2000 |
|
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 |
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 |
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 |
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
|
|
|
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 |
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 |
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 |
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 |