scholarly journals Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome

2019 ◽  
Vol 20 (15) ◽  
pp. 3813 ◽  
Author(s):  
Uri Kahanovitch ◽  
Kelsey C. Patterson ◽  
Raymundo Hernandez ◽  
Michelle L. Olsen
Keyword(s):  
Rett Syndrome ◽  
Neurodevelopmental Disorder ◽  
Genetic Mutation ◽  
Mecp2 Gene ◽  
Disease Phenotype ◽  
Intellectual Impairment ◽  
Disease Etiology ◽  
Neuronal Disease ◽  
Glial Dysfunction

Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder typically affecting females, resulting in a range of symptoms including autistic features, intellectual impairment, motor deterioration, and autonomic abnormalities. RTT is primarily caused by the genetic mutation of the Mecp2 gene. Initially considered a neuronal disease, recent research shows that glial dysfunction contributes to the RTT disease phenotype. In the following manuscript, we review the evidence regarding glial dysfunction and its effects on disease etiology.

scholarly journals Sphingolipid Metabolism Perturbations in Rett Syndrome

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 221 ◽  
Author(s):  
Cappuccio ◽  
Donti ◽  
Pinelli ◽  
Bernardo ◽  
Bravaccio ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Metabolic Profiling ◽  
Neurodevelopmental Disorder ◽  
Sphingolipid Metabolism ◽  
Tandem Mass ◽  
Mecp2 Gene ◽  
Loss Of Function ◽  
Disease Pathogenesis ◽  
Blood Samples ◽  
Disease Biomarkers

Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying MECP2 mutations. The metabolic profiling revealed alterations in lipids, mostly involved in sphingolipid metabolism, and sphinganine/sphingosine, that are known to have a neurotrophic role. Further investigations are required to understand the mechanisms underlying such perturbations and their significance in the disease pathogenesis. Nevertheless, these metabolites are attractive for studies on the disease pathogenesis and as potential disease biomarkers.

scholarly journals Pregnancy in a Patient with RETT SYNDROME Mutation: Dilemmas in Management

2021 ◽  
pp. 29-30
Author(s):  
Dr. Srimathy Raman ◽  
Dr. Harshala Shankar ◽  
Dr. Priyanka Shekarappa ◽  
Dr. Savitha Shirodkar ◽  
Dr. Padmalatha Venkataram
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Testing ◽  
Rett Syndrome ◽  
Pregnancy Outcomes ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Mecp2 Gene

Rett syndrome, a neurodevelopmental disorder is caused by MECP2 gene mutations inherited sporadically or x linked dominant fashion. It almost exclusively affects girls. Genetic testing can help in preventing recurrence by offering prenatal diagnosis in affected families. We discuss the case of a patient who had such a mutation and discuss her pregnancy outcomes.

scholarly journals Rett syndrome: clinical and epidemiological aspects in a Brazilian institution

2003 ◽  
Vol 61 (4) ◽  
pp. 909-915 ◽  
Author(s):  
Cristina M. Pozzi ◽  
Sergio Rosemberg
Keyword(s):  
Rett Syndrome ◽  
Clinical Data ◽  
Neurodevelopmental Disorder ◽  
Mecp2 Gene ◽  
Laboratory Studies ◽  
Cerebral Malformation ◽  
Brazilian Sample ◽  
Female Patients ◽  
Congenital Form ◽  
Frequent Finding

Rett syndrome (RS) is a neurodevelopmental disorder, preferentially found in females and specifically involving the functions on which intelligence and its expression depend - learning, hand use and speech - leaving many others intact. Mutations have been identified at Xq28 on the MECP2 gene (methyl-CpG 2), which selectively silences the expression of other genes whose location is still unknown. This is a study on clinical, diagnostic and epidemiological aspects of RS in a Brazilian sample. It included 33 female patients with chronic encephalopathy without known etiology. RS was diagnosed in 24 patients (72.7%): 17 (70.8%) had classical RS; 5 (20.8%), atypical RS and 2 (8.4%), potential RS. In 9 girls clinical data and/or laboratory studies excluded diagnosis of RS. Among the atypical RS patients, 4 were form fruste and one, congenital form. Among the girls with other encephalopathies, cerebral malformation was the most frequent finding.

scholarly journals Clinical Stringency Greatly Improves Mutation Detection in Rett Syndrome

2005 ◽  
Vol 32 (3) ◽  
pp. 321-326 ◽  
Author(s):  
Julie Gauthier ◽  
Giovana de Amorim ◽  
Gevork N. Mnatzakanian ◽  
Carol Saunders ◽  
John B. Vincent ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Rett Syndrome ◽  
Mutation Detection ◽  
Neurodevelopmental Disorder ◽  
Diagnostic Procedures ◽  
Diagnostic Tools ◽  
Mecp2 Gene ◽  
Strict Adherence ◽  
Mecp2 Mutation ◽  
The Impact

ABSTRACT:Background:Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT.Methods:Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC.Results:The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%).Conclusions:These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

Rett Syndrome

2017 ◽  
Author(s):  
C. L. Smith-Hicks ◽  
S. Naidu
Keyword(s):  
Autism Spectrum Disorders ◽  
Rett Syndrome ◽  
Clinical Phenotype ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Mecp2 Gene ◽  
Spectrum Disorders ◽  
Andreas Rett

Rett Syndrome (RTT) is a neurodevelopmental disorder that predominantly affects females but males with RTT have been identified. RTT was first described by an Austrian pediatrician, Andreas Rett. Rett syndrome was mapped to chromosome Xq28 in 1998 and a year later it was determined to be due to mutations in the MeCP2 gene at this locus. Identification of the gene led to the broadening of the clinical phenotype and further characterization into classic and atypical forms of the disease that overlap with Autism spectrum disorders during the period of regression. More than 95% of individuals with classic RTT have mutations in the MeCP2 gene.

scholarly journals Rett Syndrome: A Case Report

1970 ◽  
Vol 28 (1) ◽  
pp. 20-22
Author(s):  
MR Pathak ◽  
A Neopane
Keyword(s):  
Rett Syndrome ◽  
Speech Therapy ◽  
Neurodevelopmental Disorder ◽  
Mecp2 Gene ◽  
Dominant Inheritance ◽  
Pharmacological Agents ◽  
Developmental Regression ◽  
History Of ◽  
Social Interaction Skills ◽  
Key Words Rett Syndrome

Rett Syndrome (RS) is a neurodevelopmental disorder in which girls are predominantly affected, transmitted as an X linked dominant inheritance and caused by mutation in MECP2 gene. The basic presentation in RS is regression of previously acquired developmental milestones, lack of social interaction skills and acquired microcephaly after a certain age, which starts in early months of infancy. It is frequently misdiagnosed as autism, cerebral palsy or nonspecific developmental delay and is relatively frequent cause of delayed development in girls. Diagnosis is mainly clinical after excluding the neurodegenerative and other causes of delayed milestones. The chromosomal analysis, confirmatory tool for diagnosis is available in limited centers. The treatment is mainly speech therapy and counseling though few pharmacological agents have been tried with little response. A ten years age girl presented with the history of seizures, regression of speech and delayed motor milestones in our out patient clinic which was subsequently diagnosed as Rett Syndrome. Key Words: Rett syndrome, Developmental Regression, X Linked Dominant.    DOI = 10.3126/jnps.v28i1.1402   J. Nepal Paediatr. Soc. Vol.28(1) p.20-22

scholarly journals Rett syndrome: a neurodevelopmental disorder

2019 ◽  
Vol 6 (4) ◽  
pp. 1757
Author(s):  
Setu Dagli ◽  
Arpita Thakker Adhikari ◽  
Mona Gajre
Keyword(s):  
Genetic Testing ◽  
Developmental Delay ◽  
Rett Syndrome ◽  
X Chromosome ◽  
Genetic Disorder ◽  
Neurodevelopmental Disorder ◽  
Hand Movements ◽  
Global Developmental Delay ◽  
Mecp2 Gene ◽  
Ataxic Gait

Rett Syndrome is a rare genetic disorder caused by a mutation on the MECP2 gene on the X chromosome. It classically presents with neuroregression, loss of purposeful hand use, stereotypical involuntary hand wringing movements, an ataxic gait and acquired microcephaly with a large proportion of patients developing seizures. The authors present the case of a 3.5 year old girl with severe global developmental delay and regression, loss of purposeful hand use and an ataxic gait for 2 years and seizures since 5 days along with microcephaly with involuntary hand movements but no classic wringing movements with no significant findings on MRI and EEG and diagnosed with Rett Syndrome on the basis of genetic testing.

scholarly journals Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome

2021 ◽  
Vol 22 (8) ◽  
pp. 4240
Author(s):  
Cinzia Signorini ◽  
Silvia Leoncini ◽  
Thierry Durand ◽  
Jean-Marie Galano ◽  
Alexandre Guy ◽  
...  
Keyword(s):  
Disease Progression ◽  
Gene Mutation ◽  
Rett Syndrome ◽  
Neurodevelopmental Disorder ◽  
Biological Significance ◽  
Clinical Severity ◽  
Stage Ii ◽  
Disease Stage ◽  
Mecp2 Gene ◽  
Mecp2 Mutation

Neuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001); (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X); (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002); and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype–phenotype associations in RTT.

scholarly journals Clinical Evaluation of Patients with Classical Rett Syndrome and MECP2 Gene Analysis

2021 ◽  
Vol 35 (1) ◽  
pp. 87-97
Author(s):  
Filiz Hazan ◽  
Semra Gürsoy ◽  
Aycan Ünalp ◽  
Ünsal Yılmaz
Keyword(s):  
Rett Syndrome ◽  
Clinical Evaluation ◽  
Gene Analysis ◽  
Mecp2 Gene
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