Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Mullegama, Sureni V; Elsea, Sarah H.

doi:10.1038/ejhg.2016.35

Cited by 35 publications

(43 citation statements)

References 33 publications

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“…Disruption of MBD5 gene, encoding a member of the methyl‐CpG‐binding domain (MBD) protein family results in SMS‐like phenotype . MBD5 haploinsufficiency is responsible for the phenotype of the 2q23.1 deletion syndrome (MRD1) which has also been shown to result by point mutation . The idea that MBD5 might exert a control on RAI1 transcription has been supported by the finding of RAI1 downregulation in patients with 2q23.1 deletion .…”

Section: Smith‐magenis and Related Disordersmentioning

confidence: 90%

“…52 53 MBD5 haploinsufficiency is responsible for the phenotype of the 2q23.1 deletion syndrome (MRD1) which has also been shown to result by point mutation. 54,55 The idea that MBD5 might exert a control on RAI1 transcription has been supported by the finding of RAI1 downregulation in patients with 2q23.1 deletion. 56 Further studies correlate MBD5 haploinsufficiency of patients LCLs to downregulation of Clock Circadian genes as well as of RAI1, thus linking circadian rhythms impairment to RAI1 expression.…”

Section: Chromatin Dysregulation At the Roots Of Dd/id Syndromesmentioning

confidence: 98%

“…58 These roles are accomplished by dynamic interactions with transcription factors and neuronal chromatin. As BDMR patients show RAI1 downregulation, [54][55][56][57][58][59] it might be posited that HDAC4 plays as RAI1 transcriptional regulator, outlining that the 2 genes belong to the same network, accounting for the shared clinical signs of the 2 syndromes.…”

Section: Chromatin Dysregulation At the Roots Of Dd/id Syndromesmentioning

confidence: 99%

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Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms

Larizza

Finelli

2018

Clinical Genetics

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Advances in genomic analyses based on next-generation sequencing and integrated omics approaches, have accelerated in an unprecedented way the discovery of causative genes of developmental delay (DD) and intellectual disability (ID) disorders. Chromatin dysregulation has been recognized as common pathomechanism of mendelian DD/ID syndromes due to mutation in genes encoding chromatin regulators referred as transcriptomopathies or epigenetic disorders. Common to these syndromes are the wide phenotypic breadth and the recognition of groups of distinct syndromes with shared signs besides cognitive impairment, likely mirroring common molecular mechanisms. Disruption of chromatin-associated transcription machinery accounts for the phenotypic overlap of Cornelia de Lange with KBG and with syndromes of the epigenetic machinery. The genes responsible for Smith-Magenis-related disorders act in interconnected networks and the molecular signature of histone acetylation disorders joins Rubinstein-Taybi-related syndromes. Deciphering pathway interconnection of clinically similar ID syndromes may enhance search of common targets useful for developing new therapeutics.

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Section: Smith‐magenis and Related Disordersmentioning

confidence: 90%

Section: Chromatin Dysregulation At the Roots Of Dd/id Syndromesmentioning

confidence: 98%

Section: Chromatin Dysregulation At the Roots Of Dd/id Syndromesmentioning

confidence: 99%

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Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms

Larizza

Finelli

2018

Clinical Genetics

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“…). The deletion is highly penetrant and is associated with a broad phenotypic spectrum ( MBD ‐Associated Neurodevelopmental Disorders) (Mullegama and Elsea ; Camarena et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…). The clinical spectrum has been designated MBD5 ‐Associated Neurodevelopmental Disorders (MAND) (Mullegama and Elsea ). Haploinsufficiency of MBD5 (Methyl‐CpG‐binding Domain 5) (OMIM 611472) has been shown to be the cause of the phenotype associated with 2q23.1 microdeletion (Williams et al.…”

Section: Introductionmentioning

confidence: 99%

Inherited 2q23.1 microdeletions involving the MBD5 locus

Tadros

Wang

Waters

et al. 2017

Mol Genet Genomic Med

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BackgroundMicrodeletions of 2q23.1 disrupting MBD5 and loss of function mutations of MBD5 cause MBD5‐Associated Neurodevelopmental disorders (MAND). Nearly all reported patients have been isolated cases of de novo origin.MethodsThis study investigates three families with inherited MBD5 mutations from three different Regional Genetics Centres in the UK.ResultsTwo of the parents in the study had MBD5 deletions in a mosaic form. The parent with an MBD5 deletion in an apparently nonmosaic form has a psychiatric disorder in the absence of developmental delay or dysmorphism.ConclusionsInherited forms of MBD5 deletions are rare, but do occur, especially in a mosaic form. The phenotypic spectrum of MAND may be wider than previously thought.

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MBD5‐related intellectual disability in a Vietnamese child

2021

American J of Med Genetics Pt A

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The disruption of methyl‐binding domain protein 5 (MBD5) gene has been determined as a significant cause of a group of disorders known as MBD5‐associated neurodevelopmental disorder. Here, we report a novel pathogenic mutation, NM_001378120.1 (MBD5): c.217‐1G>C, occurring at the acceptor splicing site of intron 6 of the MBD5 gene identified in a Vietnamese child with intellectual disability, autistic‐like behaviors, and seizure. Phenotypic manifestations in this patient are highlighted with neurodevelopmental impairments whereas his facial dysmorphism is unremarkable. Our finding has enriched the understanding of the spectrum of MBD5 variants, a critical database for diagnosis, genetic counseling, and management of the patients with neurological diseases.

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Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND)

Cited by 35 publications

References 33 publications

Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms

Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms

Inherited 2q23.1 microdeletions involving the MBD5 locus

MBD5‐related intellectual disability in a Vietnamese child

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