MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.
Linyan MengPirjo IsohanniYunru ShaoBrett H GrahamScott E HickeyStephanie BrooksAnu SuomalainenPascal JosetKatharina SteindlAnita RauchAnnette HackenbergFrances A HighAmy Armstrong-JavorsNiccolò E MencacciPaulina Gonzàlez-LatapiWalaa A KamelJasem Y Al-HashelBernabé I BustosAlejandro V HernandezDimitri KraincSteven J LubbeHilde Van EschChiara De LucaKatleen BallonClaudia RavelliLydie BurglenLeila QebiboDaniel G CalameTadahiro MitaniDana MarafiDavut PehlivanNebal W SaadiYavuz SahinReza MaroofianStephanie EfthymiouHenry HouldenShazia MaqboolFatima RahmanShen GuJennifer E PoseyJames R LupskiJill V HunterMichael F WanglerChristopher J CarrollYaping YangPublished in: Annals of neurology (2021)
The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021;89:828-833.
Keyphrases
- intellectual disability
- copy number
- autism spectrum disorder
- end stage renal disease
- case report
- genome wide
- newly diagnosed
- transcription factor
- ejection fraction
- spinal cord injury
- peritoneal dialysis
- prognostic factors
- deep brain stimulation
- dna methylation
- minimally invasive
- induced pluripotent stem cells
- botulinum toxin
- cerebral palsy