Homozygosity for MECP2 gene in a girl with classical Rett syndrome

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.

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Identification and characterization of novel sequence variations in MECP2 gene in Rett syndrome patients

Brain and Development ◽

10.1016/j.braindev.2009.11.007 ◽

2010 ◽

Vol 32 (10) ◽

pp. 843-848 ◽

Cited By ~ 7

Author(s):

Leila Schuindt Monnerat ◽

Aline dos Santos Moreira ◽

Maria Carolina Viana Alves ◽

Cibele Rodrigues Bonvicino ◽

Fernando Regla Vargas

Keyword(s):

Rett Syndrome ◽

Mecp2 Gene ◽

Sequence Variations ◽

Identification And Characterization

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A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients

Human Genetics ◽

10.1007/s004390000422 ◽

2001 ◽

Vol 108 (1) ◽

pp. 43-50 ◽

Cited By ~ 54

Author(s):

Violaine Bourdon ◽

Christophe Philippe ◽

Orianne Labrune ◽

Daniel Amsallem ◽

Cécile Arnould ◽

...

Keyword(s):

Detailed Analysis ◽

Rett Syndrome ◽

Mecp2 Gene ◽

Dna Rearrangements ◽

Recurrent Mutations

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ESOPHAGEAL MOTILITY DISTURBANCES IN CHILDREN WITH RETT SYNDROME: CORRELATION WITH X-LINKED METHYL CPG BINDING PROTEIN (MECP2) GENE MUTATIONS

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/01.mpg.0000181946.55344.ff ◽

2005 ◽

Vol 41 (4) ◽

pp. 520-521 ◽

Cited By ~ 1

Author(s):

John E Fortunato ◽

Anil Darbari ◽

John Desbiens ◽

Geni Bibat ◽

Sakkubai Naidu ◽

...

Keyword(s):

Rett Syndrome ◽

Esophageal Motility ◽

Binding Protein ◽

Gene Mutations ◽

Mecp2 Gene ◽

Protein Mecp2

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Genomic analyses in a large clinical cohort reveal high prevalence of MECP2 variants associated with neuropsychiatric phenotypes in adulthood

10.1101/2021.05.31.21257498 ◽

2021 ◽

Author(s):

Claudia Gonzaga-Jauregui ◽

Alina Kurolap ◽

Lauren Walsh ◽

Jeffrey Staples ◽

Cristopher Van Hout ◽

...

Keyword(s):

Major Depression ◽

Rett Syndrome ◽

Clinical Care ◽

Clinical Information ◽

Neuropsychiatric Disorders ◽

Mecp2 Gene ◽

Sequencing Data ◽

Clinical Cohort ◽

Pathogenic Variants ◽

Increased Risk

Abstract Purpose: To evaluate the phenotypes of individuals with pathogenic and likely pathogenic variants in the MECP2 gene. Methods: We surveyed exome sequencing data from a large clinical care cohort for deleterious variation in the MECP2 gene. We reviewed de-identified clinical information for these individuals to interrogate for neurodevelopmental and neuropsychiatric phenotypes. Results: We identified pathogenic and likely pathogenic variants in MECP2 in individuals with typical and atypical Rett syndrome, and neuropsychiatric phenotypes, and estimate a prevalence of MECP2-associated disorders of 1 in 2,645 individuals. We observed a 7.45x increased relative risk of neuropsychiatric phenotypes, especially major depression, in adult individuals with deleterious variants in MECP2 without a diagnosis of Rett syndrome. Male individuals with missense pathogenic variants in MECP2 appear to have more severe neuropsychiatric phenotypes. Conclusions: We identified and report individuals with heterozygous pathogenic variants in MECP2 and their phenotypes in a large clinical cohort. The observed prevalence of MECP2-associated disorders in our cohort is higher than estimated in the literature. Individuals with pathogenic variants in MECP2 can survive into adulthood but are at increased risk of developing neuropsychiatric disorders, mainly major depression. Pathogenic variation in MECP2 is a likely important contributor to neuropsychiatric disorders in the general population.

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Rett syndrome in Russia and abroad: a scientific historical review

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2020-65-3-25-31 ◽

2020 ◽

Vol 65 (3) ◽

pp. 25-31

Author(s):

S. G. Vorsanova ◽

Yu. B. Yurov ◽

V. Yu. Voinova ◽

I. Yu. Yurov

Keyword(s):

Rett Syndrome ◽

Rare Diseases ◽

Gene Sequence ◽

Genetic Diseases ◽

Historical Review ◽

Mecp2 Gene ◽

Cellular Mechanisms ◽

Rare Genetic Diseases ◽

Present Information ◽

Genomic Disorders

This review presents the theoretical, practical and geographical aspects of Rett syndrome and other rare diseases, according to the data of the last VIII International Congress in Russia, and the main publications on Rett syndrome. The issues highlighted by the participants remain relevant and determine the direction of modern studies. The presentations made at the symposium helped to form a global concept of the molecular and cellular mechanisms of Rett syndrome and a number of rare genetic/genomic diseases. The article presents a number of domestic findings in the field of Rett syndrome and other rare diseases. The authors also present information on rare diseases associated with the Rett-like-phenotype or with mutations/variations of the MECP2 gene sequence copies. The authors consider the identified chromosomal (genomic) disorders / diseases in the context of rare diseases. This approach to the Rett syndrome studies analysis is quite new in the world research practice. We hope this review to become valuable not only for specialists in the field of rare genetic diseases, but also for the scientists and clinicians studying Rett syndrome and for physicians (pediatricians, geneticists, neurologists, psychiatrists) meeting these patients in their practice.

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