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A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

ABSTRACT: BACKGROUND:The minimal critical region in 2q23.1 deletion syndrome comprises one gene only, that is, the methyl-CpG-binding domain protein 5 (MBD5) gene. Since the phenotypes of patients with deletions, duplications or pathogenic variants of MBD5 show considerable overlap, the term MBD5-associated neurodevelopmental disorder (MAND) was proposed. These syndromes are characterized by intellectual disability, seizures of any kind and symptoms from the autism spectrum. In a very limited number of patients, MAND may be associated with regression starting either at early infancy or at midlife. METHODS:The present paper describes a severely intellectually disabled autistic female with therapy resistant complex partial epilepsy starting at her 16the with gradual cognitive and behavioral regression towards her sixth decade. RESULTS:Cognitive and behavioral regression occurred towards the patient's sixth decade. Exome sequencing disclosed a novel heterozygous pathogenic frameshift mutation of MBD5 that was considered to be causative for the combination of intellectual disability, treatment-resistant epilepsy and autism. CONCLUSION:The presented patient is the second with a pathogenic MBD5 mutation in whom the course of disease is suggestive of early onset dementia starting in her fifth decade. These findings stress the importance of exome sequencing, also in elderly intellectually disabled patients, particularly in those with autism.

SUBMITTER: Verhoeven W

PROVIDER: S-EPMC6687664 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

Verhoeven Willem W Egger Jos J Kipp Janneke J Verheul-Aan de Wiel Jiska J Ockeloen Charlotte C Kleefstra Tjitske T Pfundt Rolph R

Molecular genetics & genomic medicine 20190709 8

<h4>Background</h4>The minimal critical region in 2q23.1 deletion syndrome comprises one gene only, that is, the methyl-CpG-binding domain protein 5 (MBD5) gene. Since the phenotypes of patients with deletions, duplications or pathogenic variants of MBD5 show considerable overlap, the term MBD5-associated neurodevelopmental disorder (MAND) was proposed. These syndromes are characterized by intellectual disability, seizures of any kind and symptoms from the autism spectrum. In a very limited numb ...[more]

PMID: 31290275

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Project description:BACKGROUND:Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials. OBJECTIVE:We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients. METHODS:We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2). RESULTS:Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups. CONCLUSION:We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.

Project description:BackgroundPoor self-care skills and personal hygiene resulted from limitations in learning and understanding, put intellectually disabled individuals at greater risk for intestinal parasitic infections (IPIs). Despite several regional reports in Iran, the overall burden on IPIs among intellectually disabled individuals is poorly understood. Hence, the present study aimed to estimate the pooled prevalence of IPIs among intellectually disabled individuals in Iran.MethodsUsing the PRISMA guidelines, we conducted a systematic review and meta-analysis of data retrieved from seven electronic databases (PubMed, Web of Science, Scopus, Embase, and ProQuest for English articles, as well as SID and Magiran for Persian) from their inception up to December 2020. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI) and depicted as a forest plot, while heterogeneity was evaluated using Cochran's Q-test.ResultsExactly 1263 of the 3004 intellectually disabled individuals examined by 14 studies across 10 provinces of Iran were positive for IPIs. Overall pooled prevalence estimate was 41% (95% CI 29-53%) with a range of 21% (95% CI 10-32%) to 68% (95% CI 55-80%) across sub-groups. Entamoeba coli (16.2%; 95% CI 10.3-22%), Blastocystis spp. (12.2%; 95% CI 7.2-17.2%), and Giardia duodenalis (11.9%; 95% CI 7.4-16.3%) were the most prevalent protozoan species. In terms of helminthic agents, the most prevalent species were Enterobius vermicularis (11.3%; 95% CI 6.3-16.3%) followed by Strongyloides stercoralis (10.9%; 95% CI 5.0-16.9%) and Hymenolepis nana (2.8%; 95% CI 0.4-5.2%) CONCLUSION: IPIs are highly prevalent among intellectually disabled individuals in Iran. Improving the health status and implementing infectious disease prevention strategies in rehabilitation centers, health promotion interventions to improve personal hygiene of intellectually disabled individuals, as well as utilize sensitive diagnostic methods besides routine stool examination techniques, and treatment of infected individuals will help in the control of these infections among intellectually disabled individuals.

Dataset Information

A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

Publications

A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

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