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

BACKGROUND: Rett syndrome (RS) is a severe neurodevelopmental X-linked dominant disorder caused by mutations in the MECP2 gene. PURPOSE: To search for point mutations on the MECP2 gene and to establish a correlation between the main point mutations found and the phenotype. METHOD: Clinical evaluation of 105 patients, following a standard protocol. Detection of point mutations on the MECP2 gene was performed on peripheral blood DNA by sequencing the coding region of the gene. RESULTS: Classical RS was seen in 68% of the patients. Pathogenic point mutations were found in 64.1% of all patients and in 70.42% of those with the classical phenotype. Four new sequence variations were found, and their nature suggests patogenicity. Genotype-phenotype correlations were performed. CONCLUSION: Detailed clinical descriptions and identification of the underlying genetic alterations of this Brazilian RS population add to our knowledge of genotype/phenotype correlations, guiding the implementation of mutation searching programs.

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Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms

Journal of Human Genetics ◽

10.1007/s10038-007-0121-x ◽

2007 ◽

Vol 52 (4) ◽

pp. 342-348 ◽

Cited By ~ 17

Author(s):

Daniela Zahorakova ◽

Robert Rosipal ◽

Jan Hadac ◽

Alena Zumrova ◽

Vladimir Bzduch ◽

...

Keyword(s):

Rett Syndrome ◽

Mutation Analysis ◽

Mecp2 Gene ◽

Novel Mutations

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Rett syndrome and the MECP2 gene

Journal of Medical Genetics ◽

10.1136/jmg.38.4.217 ◽

2001 ◽

Vol 38 (4) ◽

pp. 217-223 ◽

Cited By ~ 26

Author(s):

T. Webb

Keyword(s):

Rett Syndrome ◽

Mecp2 Gene

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Influence of MECP2 Gene Mutation and X-Chromosome Inactivation on the Rett Syndrome Phenotype

Journal of Child Neurology ◽

10.1177/08830738040190070501 ◽

2004 ◽

Vol 19 (7) ◽

pp. 503-508 ◽

Cited By ~ 14

Author(s):

Jong Hee Chae ◽

Hee Hwang ◽

Yong Seung Hwang ◽

Hee Jung Cheong ◽

Ki Joong Kim

Keyword(s):

Gene Mutation ◽

Rett Syndrome ◽

X Chromosome ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Mecp2 Gene

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Sphingolipid Metabolism Perturbations in Rett Syndrome

Metabolites ◽

10.3390/metabo9100221 ◽

2019 ◽

Vol 9 (10) ◽

pp. 221 ◽

Cited By ~ 1

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.

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