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Genetic Studies

Below is a list of relevant research articles on MBD5 associated neurodevelopmental disorder (MAND) and Complex 3 Mitochondrial Disease, along with brief overviews of each. These articles are listed based on their relevance to MBD5 and CYTB, focusing on clinical phenotypes, molecular mechanisms, and genetic findings related to these conditions. I will update this page when I discover new research as long as I am able to. 

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Genetic Studies (Organized by Clinical Diagnosis)

Seizures in MAND

These articles focus on epilepsy and seizure disorders associated with MBD5 disruptions, relevant to the seizures experienced by myself and my daughters.

Phenotypic Spectrum of Seizure Disorders in MAND

Details seizure patterns in 23 MAND patients, with onset around 2.9 years, including generalized tonic-clonic, focal, and myoclonic seizures. Some experienced status epilepticus. This aligns with our family’s seizures, offering a focus for epilepsy research in MAND.

URL: https://www.neurology.org/doi/10.1212/NXG.0000000000000579

Potential Implications on Neural Primary Cilia

A MBD5 variant in a 12-year-old with drug-resistant seizures, developmental delay, and Rett-like features. Neural progenitor cells showed ciliary defects, suggesting MBD5’s role in ciliary function. Researchers can explore if ciliary dysfunction contributes to our neurological symptoms, including seizures.

URL: https://www.mdpi.com/1422-0067/24/16/12603 

Adult Female Patient with Epilepsy: Suggestive of Early Onset Dementia

Reports an adult with an MBD5 frameshift mutation, presenting epilepsy, intellectual disability, autism, and regression in her 50s, possibly early-onset dementia. This mirrors my late-onset seizures and memory loss, providing a research avenue for epilepsy and regression in MAND.

URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC6687664/


Autism Spectrum Disorder (ASD) and Behavioral Phenotypes

These articles emphasize MBD5’s role in autism spectrum disorder and related behavioral challenges, which may connect to my family’s neurodevelopmental symptoms.

MBD5 Contributes Spectrum Psychopathology Neurodevelopmental Abnormalities

Explores how MBD5 disruptions (deletions, duplications) lead to intellectual disability, ASD, and behavioral challenges. It highlights MBD5’s role in brain development, offering researchers a chance to investigate its impact on our family’s neurological symptoms.

URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC4756476/

Role for MBD5 in Autism Spectrum Disorder

Compares 2q23.1 deletions and duplications, showing both cause ASD, with deletions leading to more severe symptoms like seizures. Researchers can explore how MBD5 dosage affects our family’s neurodevelopmental profile.

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865402/ 

MBD5 Associated with Autism Spectrum Disorders and Schizophrenia Phenotypes

Resequences MBD5 in 562 Japanese patients, finding 16 rare SNVs linked to autism and schizophrenia. This suggests MBD5’s role in a broad neurodevelopmental spectrum, encouraging researchers to explore additional symptoms in our family.

URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC5159472/

MAND Neural Progenitor Cells Dysregulation of Autism Associated Genes

Identifies 468 differentially expressed genes in MAND neural cells, including 20 linked to ASD, affecting pathways like TGFβ. This molecular insight could guide research into our neurological symptoms and potential mitochondrial overlaps.

URL: https://www.nature.com/articles/s41598-021-90762-3


Intellectual Disability and Neurodevelopmental Abnormalities

These articles focus on intellectual disability, developmental delays, and other neurodevelopmental features, which align with my youngest daughter’s in utero symptoms and our shared MBD5 deletion challenges.

MBD5 as a Single Causal Locus of Intellectual Disability, Epilepsy, and ASD

Establishes MBD5 as the key gene in 2q23.1 microdeletion syndrome, now recognized as MAND, linking it to intellectual disability, epilepsy, and Autism Spectrum Disorder. This foundational study can help researchers understand my youngest daughters developmental delays and our seizures.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3188839/

Extended Spectrum of MBD5 Mutations in Neurodevelopmental Disorders

 Identifies new de novo MBD5 mutations (deletions, duplications, nonsense) in patients with intellectual disability, language impairment, and autism-like symptoms. Researchers can investigate if rare variants like our non-coding MBD5 deletion contribute to our severe phenotypes.

URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831065/ 

A Molecular Model for Neurodevelopmental Disorders

Investigates MBD5 and SATB2 in neural stem cells, showing MBD5 reduction affects cell proliferation and neural differentiation. This offers a framework for researchers to study how MBD5 impacts brain development in our family.

URL:https://pmc.ncbi.nlm.nih.gov/articles/PMC4471287/Disorders


Sleep Disturbances and Circadian Dysregulation

This article highlights sleep issues in MAND, which may connect my family’s challenges with sleep disturbances, as noted in prior MAND studies.

MAND Is Associated with Sleep Disturbance and Disrupts Circadian Pathways

Finds that MAND disrupts sleep and circadian pathways in 2q23.1 deletion patients, affecting 90% of MAND cases. Common to Smith-Magenis and Fragile X Syndromes. Researchers can study these pathways to address our family’s sleep issues. Both my daughters and I have had lifelong issues of falling and staying asleep. I was diagnosed with Central Sleep Apnea around the same time my seizures started 2 years ago. My youngest has Obstructive Sleep Apnea. 

URL: https://pubmed.ncbi.nlm.nih.gov/25271084/


Non-Coding Genes and Regions Impacting Mitochondrial Function in Disease

These articles explore how non-coding genes or regions (e.g., ncRNAs, non-coding mtDNA variants, regulatory elements) affect mitochondrial function in disease, with a focus on studies involving the CYTB gene, relevant to my family’s CYTB variant and mitochondrial dysfunction.

Mitochondria Encoded Non-Coding RNAs in Cell Physiology

This study identifies mtDNA encoded ncRNAs, including lncCyt b, transcribed from the CYTB gene region, which forms RNA-RNA duplexes to stabilize mitochondrial mRNAs or regulate gene expression. They are tissue specific and influence oxidative phosphorylation. Our non-coding mtDNA variants might produce similar ncRNAs that impact CYTB function, offering a research angle for our mitochondrial dysfunction.

URL: https://www.frontiersin.org/journals/cell-a

Mitochondrial Non-Coding RNAs Are Potential Mediators of Mitochondrial Home

This article highlights mitochondrial ncRNAs, both mtDNA encoded and nuclear encoded, that regulate mito gene expression and protein import. The lncCyt b (long non-coding RNA from the CYTB gene) can shuttle to the nucleus, potentially affecting mito-nuclear communication and oxidative phosphorylation, processes disrupted in mitochondrial disease. This is directly relevant to our family’s case, as lncCyt b may influence CYTB expression.

URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC9775270/

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