Publications by authors named "Grace Vassallo"

Article Synopsis
  • New diagnostic criteria for NF2-related schwannomatosis were established in 2022, leading to an updated prevalence study in the UK, which focused on the rate of de novo NF2 cases.
  • A total of 1,084 living NF2 patients were identified, indicating a prevalence of 1 in 61,332, with a striking 72% of cases being de novo, many of which were mosaic.
  • The findings also revealed that nonsense variants were most common (24.8%), while missense variants had a higher familial association (56%), emphasizing the importance of patient databases for accurate genetic counseling.
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Background: Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP).

Methods: All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis.

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Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as autism. GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1.

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Adenylosuccinase deficiency is a rare inborn error of metabolism. We present a newborn who died at 52 days of age with clinical features suggestive of severe epileptic encephalopathy and leukodystrophy of unknown cause. Post-mortem examination showed an unusual vacuolar appearance of the brain.

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Introduction: Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition.

Methods: 29 adolescents aged 11-17 years were compared to age and sex-matched controls.

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Neurofibromatosis type 1 (NF1) can affect multiple systems in the body. An under recognised phenotype is one of muscle weakness. Clinical studies using dynamometry and jumping mechanography have demonstrated that children with NF1 are more likely to have reduced muscle force and power.

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We report on the location, symptoms, and management of plexiform neurofibroma (PN) in children with Neurofibromatosis Type 1 (NF1) attending the 2 National Complex Neurofibromatosis 1 Services at Guy's and St. Thomas' NHS Foundation Trust, London and St Mary's Hospital, Manchester. Retrospective data collection was performed from patient chart reviews from April 2018 to April 2019.

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The impact of the Neurofibromatosis type 1 (NF1) on cognition have been subject to much clinical investigation, but environmental modifiers of disease expression have not yet been systematically investigated. The aim of this paper is to determine the role of demographic and environmental factors such as age, sex, socioeconomic status, parental NF1 status and neurological complications on the cognitive, behavioural and academic outcomes in NF1. Participants included 206 children aged 4-18 years seen within the Manchester clinical research NF1 service.

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Neurofibromatosis 1 (NF1) is a single gene disorder associated with working Memory (WM) impairments. The aim of this study was to investigate P300 event-related potential (ERP) associated with WM in NF1. Sixteen adolescents with NF1 were compared with controls on measures of WM and EEG was recorded during a WM nback task.

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Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. Girls with a recurrent de novo c.3013C>T; p.

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Background: Limited data exist on the disease course of neurofibromatosis type 2 (NF2) to guide clinical trial design.

Methods: A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990 and 2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred, and inheritance type.

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Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE).

Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies.

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Neurofibromatosis type 1 (NF1) manifests itself in many ways in the spine. This study aims to report the types of spinal lesions, clinical and demographic data in a large cohort from a complex NF1 centre. The characteristics of those with spinal neurofibromatosis, where neurofibromas are present on every spinal nerve root, were sought for comparison with the wider group of NF1 patients.

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Objectives: Aqueduct stenosis (AS) and fourth ventricle outflow obstruction are rare associations of neurofibromatosis type 1 (NF1), resulting in ventriculomegaly and hydrocephalus requiring surgical treatment. This study aims to identify the prevalence of AS and its patterns of clinical presentation, aetiology and treatment in the paediatric complex NF1 population.

Patients And Methods: Patients with NF-1 aged 0-18 years were recruited from the Regional Genetic Family Register, following institutional review board approval.

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Aim: This study describes the prevalence and severity of perceived fatigue in a young neurofibromatosis type 1 (NF1) population.

Methods: Ethical approval was obtained and NF1 affected Individuals aged 2-18 years from the Manchester's NF1 clinic invited along with any unaffected siblings. The PedsQL Multidimensional Fatigue Scale Parental and child report was used.

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Background: A homozygous founder mutation in /, encoding mitochondrial poly(A) polymerase (MTPAP), was first reported in six individuals of Old Order Amish descent demonstrating an early-onset, progressive spastic ataxia with optic atrophy and learning difficulties. MTPAP contributes to the regulation of mitochondrial gene expression through the polyadenylation of mitochondrially encoded mRNAs. Mitochondrial mRNAs with severely truncated poly(A) tails were observed in affected individuals, and mitochondrial protein expression was altered.

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Acute Encephalopathy with Reduced Subcortical Diffusion or AED is a unique subtype of acute paediatric encephalopathy which presents with altered mental status, prolonged seizures and developing characteristic radiological signal changes within the subcortical white matter. Reports of such cases have mainly been from Japan (Takanashi, 2009) and this radiological finding has been recognised as a novel feature of AED. We present three paediatric cases from a tertiary paediatric neurosciences centre in Manchester (Royal Manchester Children's hospital) with characteristic subcortical signal change, and furthermore, follow up imaging which in all 3 patients demonstrated a varying degree of cerebral atrophy.

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Purpose: To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2).

Methods: Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for NF2 variants in lymphocyte DNA and where available tumor DNA. The proportion of individuals with a proven or presumed mosaic NF2 variant was assessed and allele frequencies of identified variants evaluated using next-generation sequencing.

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Childhood onset neurofibromatosis type 2 can be severe and genotype dependent. We present a retrospective phenotypic analysis of all ascertained children in England View Article and Find Full Text PDF

Objective: To describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors.

Methods: Retrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome.

Results: Eighty-eight children (median presentation age 5.

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Linear scleroderma is a characteristic form of scleroderma that typically affects children. Ocular manifestations may be present, especially when the frontoparietal area of the head is affected. We present the case of a 5-year-old boy with craniofacial linear scleroderma ("en coup de sabre") who developed exudative retinal detachment.

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Background: Mutations in the (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

Methods: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

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Article Synopsis
  • - The KCC2 protein, linked to the SLC12A5 gene, is essential for regulating chloride ions in the brain, which helps control fast synaptic inhibition.
  • - Researchers discovered mutations in the SLC12A5 gene that cause a severe form of epilepsy known as epilepsy of infancy with migrating focal seizures (EIMFS).
  • - Problems with KCC2, such as reduced surface expression and impaired function, lead to disrupted synaptic inhibition and increased neuron activity, contributing to this early-onset epilepsy.
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Article Synopsis
  • . Aicardi-Goutières syndrome is an inflammatory disease caused by mutations in seven specific genes, affecting 374 patients studied from 299 families.
  • . Patients typically present with either in utero disease onset (22.8%) or post-natal symptoms within the first year of life (68.6%), leading to severe disabilities and a high mortality rate (19.3%).
  • . A strong link was found between these genetic mutations and increased type I interferon activity, suggesting a need for targeted treatment strategies to address the serious health issues associated with the syndrome.
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Importance: Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease.

Objective: To determine the molecular basis of multiple respiratory chain complex deficiencies.

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