MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

Abstract

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

MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia

“…Both SLC6 transportopathies and inherited disorders of GPI deficiency are associated with a broad range of neurological diseases. 26,27 Early neuroimaging abnormalities in our patients are similar to those described in MED27-related disease 6 and GPI deficiency disorders with cerebellar defects and white matter changes. 27 To date, the later imaging findings in the older sibling have not been reported in MED27 disease.…”

High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population

“…Among these genes, 14 were found to have variants in two or more families (AMPD2 [2; MIM: 102771], AP3B2 [2; MIM: 602166], CLP1 [4; MIM: 608757], DDC [2; MIM: 107930], FOXG1 [2; MIM: 164874], GRM7 [2; MIM: 604101], LAMA1 [2; MIM: 150320], LARP7 [2; MIM: 612026], LPAR6 [2; MIM: 609239], PARD3B [2; MIM: 619353], 52 RNASEH2A [2; MIM: 606034], SNX14 [2; MIM: 616105], TBC1D23 [2; MIM: 617687], and WDR81 [2; MIM: 614218]). Placing these findings in the larger context of our full NDD cohort, which includes TBM1, 13 TBM2, and several additional case and cohort reports, [53][54][55][56][57][58][59][60][61][62][63] there are 185 known NDD-associated genes that contribute to a total of 218 molecular diagnoses.…”

Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology

“…It is located in the junction of the Head and Tail of the MED complex ( Figure 3 ) and interacts with MED29, which in turn interacts with MED14 to link the Tail module with the Head and Middle modules ( Figure 3 ). Though the specific biological functions of MED27 are unknown yet, it clearly plays an essential role in early embryonic and neuronal development [ 80 , 81 ]. MED27 has been found that is highly expressed in BC tissues and cells and its expression correlates with tumor size and grade and the high expression of MED27 had a poor prognosis [ 82 ].…”