Preserved speech variants of the Rett syndrome: Molecular and clinical analysis

Zappella, Michele; Meloni, Ilaria; Longo, Ilaria; Hayek, Joussef; Renieri, Alessandra

doi:10.1002/ajmg.10005

Cited by 119 publications

(121 citation statements)

References 24 publications

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“…In females, the phenotypes might range from mild learning disabilities to autism, tremors, and anxiety. This is mainly due to variation in patterns of X-chromosome inactivation (XCI) (Christodoulou and Ho 1993;Zappella et al 2001;Huppke et al 2006;Lasalle and Yasui 2009).…”

Section: Clinical Features and Phenotypic Spectrummentioning

confidence: 99%

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

Zoghbi

Bear

2012

Cold Spring Harbor Perspectives in Biology

665

589

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The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits.

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Section: Clinical Features and Phenotypic Spectrummentioning

confidence: 99%

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

Zoghbi

Bear

2012

Cold Spring Harbor Perspectives in Biology

665

589

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“…Zappella et al 25 noted that early truncating mutations of MECP2 lead to a poor prognosis (classic RTT), whereas late truncating missense mutations lead either to classic RTT or to preserved speech variant. Early truncating mutations were associated with a more severe course of the disorder.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

et al. 2010

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Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C4T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G4T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G4T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations.

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“…населения [12,26]. Среди наиболее частых вариантов синдрома Ретта превали-рует вариант с сохранной речью [42].…”

Section: исключающие синдром ретта диагностические кри-терииunclassified

Rett Syndrome: Difficulties of Diagnostics (Clinical and Psychopathological Aspects)

Малинина¹,

Zabozlaeva²

2016

Rus. ž. det. nevrol.

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Preserved speech variants of the Rett syndrome: Molecular and clinical analysis

Cited by 119 publications

References 24 publications

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

Rett Syndrome: Difficulties of Diagnostics (Clinical and Psychopathological Aspects)

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