Inherited 2q23.1 microdeletions involving the MBD5 locus
Shereen Tadros1, Rubin Wang1, Jonathan J Waters1
1North East Thames Regional Genetics ServiceGreat Ormond Street HospitalLondonWC1N 3JHUK.
Background:
Microdeletions 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.
Methods:
This study investigates three families with inherited MBD5 mutations from three different Regional Genetics Centres in the UK.
Results:
Two 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.
Conclusions:
Inherited 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.
Insights
Inherited MBD5 deletions causing MBD5-Associated Neurodevelopmental Disorders (MAND) are rare but occur, often in mosaic form. This suggests a broader spectrum of MAND phenotypes than previously recognized.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Human Genetics
Background:
- MBD5 gene mutations and 2q23.1 microdeletions cause MBD5-Associated Neurodevelopmental Disorders (MAND).
- Most previously identified cases originated as de novo events.
- The genetic basis and inheritance patterns of MAND require further investigation.
Purpose of the Study:
- To investigate inherited MBD5 mutations within families.
- To explore the phenotypic spectrum of MBD5-Associated Neurodevelopmental Disorders (MAND) in inherited cases.
- To determine the frequency and presentation of mosaic MBD5 deletions.
Main Methods:
- Analysis of three families with inherited MBD5 mutations.
- Genetic testing across multiple generations within affected families.
- Clinical assessment of individuals with MBD5 deletions.
Main Results:
- Identified inherited MBD5 deletions in three families.
- Observed mosaic MBD5 deletions in two parents.
- One parent with an apparently non-mosaic MBD5 deletion presented with psychiatric disorder, without developmental delay or dysmorphism.
Conclusions:
- Inherited MBD5 deletions, particularly mosaic forms, are a rare but recognized cause of MBD5-Associated Neurodevelopmental Disorders (MAND).
- The phenotypic spectrum of MAND is broader than previously understood, encompassing psychiatric disorders.
- Mosaic inheritance should be considered in the genetic evaluation of suspected MAND cases.
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