MED23‐associated intellectual disability in a non‐consanguineous family

Abstract

Intellectual disability (ID) is a heterogeneous condition arising from a variety of environmental and genetic factors. Among these causes are defects in transcriptional regulators. Herein, we report two brothers in a non-consanguineous family with novel compound heterozygous, disease-segregating mutations (NM_015979.3: [3656A>G];[4006C>T], NP_057063.2: [H1219R];[R1336X]) in MED23. This gene encodes a subunit of the Mediator complex that modulates the expression of RNA polymerase II-dependent genes. These brothers, who had profound ID, spasticity, congenital heart disease, brain abnormalities, and atypical electroencephalography, represent the first case of MED23-associated ID in a non-consanguineous family. They also expand upon the clinical features previously reported for mutations in this gene.

Novel mutation in the MED23 gene for intellectual disability: A case report and literature review

“…So far, only four variants in the MED23 have been associated with an autosomal recessive form of ID and refractory epilepsy . The summary of MED23 variants is summarized in Table .…”

“…They found that the p.R617Q variant did not affect MED23 expression levels, protein stability, architecture, or composition of the whole Mediator complex, but specifically impaired the response of the JUN and the FOS , immediate‐early genes to serum mitogens . The same gene was mutated in two brothers in a nonconsanguineous family with novel compound heterozygous mutations, 3656A>G and 4006C>T, in MED23 . The patients had severe ID, spasticity, congenital heart diseases, brain abnormalities, and atypical electroencephalography.…”

“…22,28,30 So far, only four variants in theMED23 have been associated with an autosomal recessive form of ID and refractory epilepsy. 5,9,10 The summary of MED23 variants is summarized in Table 1. Hashimoto et al 5 first associated MED23 with a nonsyndromic autosomal recessive intellectual disability in five affected individuals of a consanguineous Algerian family by using homozygosity mapping and linkage analysis.…”

“…5 The same gene was mutated in two brothers in a nonconsanguineous family with novel compound heterozygous mutations, 3656A>G and 4006C>T, in MED23. 9 The patients had severe ID, spasticity, congenital heart diseases, brain abnormalities, and atypical electroencephalography. After these two reports, one patient from consanguineous parents had been reported with refractory epilepsy, which was associated with homozygous MED23 mutation.…”

“…Affected patients manifest with axial hypotonia, choreoathetosis, dystonia, Global Developmental Delay (GDD), mental retardation, microcephaly, mild to severe ID, spasticity, with or without seizure. The MRI of the brain may be normal or it may show temporal lobe hypomyelination, delayed myelination, pontine hypoplasia, and thin corpus callosum . In this study, we develop a report on an Iranian case, diagnosed with severe nonsyndromic intellectual disabilities.…”