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Mutations in MED12 cause X-linked Ohdo syndrome
Anneke T Vulto-van Silfhout1, Bert B A de Vries, Bregje W M van Bon
1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
American Journal of Human Genetics
|February 12, 2013
Summary
Mutations in the MED12 gene cause X-linked Ohdo syndrome Maat-Kievit-Brunner type, a disorder characterized by intellectual disability and distinctive facial features. This finding highlights MED12 as a key gene in Ohdo syndrome pathogenesis.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Ohdo syndrome is a group of disorders involving intellectual disability and facial anomalies, with distinct subtypes.
- The Maat-Kievit-Brunner (MKB) type is characterized by X-linked inheritance and facial coarsening in older individuals.
Purpose of the Study:
- To identify the genetic cause of Ohdo syndrome MKB type.
- To investigate the role of MED12 mutations in this specific subtype of Ohdo syndrome.
Main Methods:
- Whole exome sequencing was performed on affected males from two families with Ohdo syndrome MKB type.
- Genetic analysis was extended to include nine additional male individuals with Ohdo syndrome.
Main Results:
- Three distinct MED12 missense mutations (p.Arg1148His, p.Ser1165Pro, and p.His1729Asn) were identified in affected males across three unrelated families.
- These mutations segregated with the Ohdo syndrome MKB phenotype, indicating MED12 as the causative gene for this X-linked disorder.
Conclusions:
- Mutations in MED12 are the primary cause of X-linked Ohdo syndrome MKB type.
- Aberrant chromatin modification, potentially involving MED12, is implicated in the pathogenesis of Ohdo syndrome, alongside previously identified KAT6B mutations.
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