Brief Report: MECP2 Mutations in People Without Rett Syndrome

Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y.; Glaze, Daniel G.; Neul, Jeffrey L.

doi:10.1007/s10803-013-1902-z

Cited by 45 publications

(22 citation statements)

References 28 publications

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“…Similarly, known RTT-causing MECP2 mutations are found in patients who do not show classical RTT phenotypes (Suter et al 2013). Other than RTT, MECP2 mutations have been found in association with neurological/neuropsychiatric disorders such as, schizophrenia (Cohen et al 2002), FASD (Zoll et al 2004), PPM-X syndrome , autism , Prader-Willi syndrome (Tejada et al 2006) and Angelman syndrome (Watson et al 2001).…”

Section: Mecp2 Mutations In Non-rett Syndrome Casesmentioning

confidence: 99%

Rett Syndrome and MeCP2

2014

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Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.

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Section: Mecp2 Mutations In Non-rett Syndrome Casesmentioning

confidence: 99%

Rett Syndrome and MeCP2

2014

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“…119 We now know, as Opitz might have predicted, that much of this spectrum relates to the type of genetic mutation with the very mild variants often represented by those with C terminal deletions (see Box 2). [119][120][121] Although RTT is considered by most a clinical diagnosis there remains a fine line between the naming of individuals as "female forme fruste Rett syndrome variants" 119 or as "people without Rett syndrome." 121 The Australian register first provided the means to examine the spectrum of presentations in a total RTT population cohort using three previously published measures, designated as the Kerr, 122 Percy 123 and Pineda 124 scores.…”

Section: Overall Severity and Relationship With Genotypementioning

confidence: 99%

“…[119][120][121] Although RTT is considered by most a clinical diagnosis there remains a fine line between the naming of individuals as "female forme fruste Rett syndrome variants" 119 or as "people without Rett syndrome." 121 The Australian register first provided the means to examine the spectrum of presentations in a total RTT population cohort using three previously published measures, designated as the Kerr, 122 Percy 123 and Pineda 124 scores. 125 Considerable variability in the early regression period, current functioning and comorbidities, much of which was subsequently shown to relate to genotype, was demonstrated.…”

Section: Overall Severity and Relationship With Genotypementioning

confidence: 99%

Clinical and biological progress over 50 years in Rett syndrome

2016

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It is fifty years since Andreas Rett first described Rett syndrome, a disorder now known to be caused by a mutation in the MECP2 gene. A compelling blend of astute clinical observations, clinical and laboratory research has already built our understanding of Rett syndrome and its biological underpinnings. We document the contributions of the early pioneers and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, the lessons from both cell and animal models and how they may inform future clinical trials. With a focus on the core criteria, we examine the relationships that have been demonstrated between genotype and clinical severity. We review what is known about the many comorbidities that occur in this disorder and how genotype may also modify their presentation. We acknowledge the important drivers that are accelerating this research program including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we conclude by highlighting the major milestones since 1966 and what they mean for the day-to-day lives of those with Rett syndrome and their families. Key pointsThere has been an explosion of knowledge about Rett syndrome in relation to its genetic basis, clinical characteristics and their relationships during the fifty years since the disorder was first described by Andreas Rett.Whilst initially the diagnosis of Rett syndrome was based only on clinical criteria, identifying its genetic cause has had a major positive impact on how clinicians diagnose the disorder but also provides new challenges as we enter the era of next generation sequencing.

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“…For example, in Rett syndrome diverse mutations have been identified in the MECP2 gene (Lee et al, 2001). Moreover, some MECP2 mutations produce not Rett syndrome but other neuropsychiatric symptoms such as obsessive-compulsive disorder and attention deficit hyperactivity disorder; some individuals with well diagnosed Rett syndrome do not have MECP2 mutations at all (Suter et al, 2013). In addition, mutations in a single causative gene may only be a portal to far greater molecular complexity.…”

Section: Mendelian Brain Disordersmentioning

confidence: 99%

Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology

McCarroll

Hyman

2013

Neuron

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Advances in genome analysis, accompanied by the assembly of large patient cohorts, have made possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders.

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Brief Report: MECP2 Mutations in People Without Rett Syndrome

Cited by 45 publications

References 28 publications

Rett Syndrome and MeCP2

Rett Syndrome and MeCP2

Clinical and biological progress over 50 years in Rett syndrome

Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology

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