A de novo missense variant in MED13 in a patient with global developmental delay, marked facial dysmorphism, macroglossia, short stature, and macrocephaly

A de novo frameshift variant in MED13 gene in a patient with autism spectrum disorder and magnetic resonance imaging abnormalities mimicking tuberous sclerosis

“…Pathogenic variants of MED13 gene are known to cause neurodevelopmental disorders such as ASD, ADHD, severe speech disorders, and apraxia; a PubMed search identified only 21 patients (Boutry-Kryza et al, 2012;C Yuen et al, 2017;De Nardi et al, 2021;Kahrizi et al, 2019;Rogers et al, 2021;Snijders Blok et al, 2018;Trivisano et al, 2022). The spectrum of phenotypes emerging from the analysis of patients with variants of MED13 shows that ID of varying severity and a language disorder are the key symptoms.…”

“…A literature review (PubMed search, last search 20 September 2023) identified 21 patients with a neurological disorder due to MED13 gene involvement: five were described as single cases (De Nardi et al, 2021; Kahrizi et al, 2019; Rogers et al, 2021; Trivisano et al, 2022) including the patient carrying a 17q23.2 microdeletion including MED13 (Boutry‐Kryza et al, 2012); three were included in a cohort‐study performed with a GeneMatcher collaboration (Snijders Blok et al, 2018); the last three were identified as part of large cohorts of ASD patients in whom ES and genome sequencing (GS) were performed to identify new candidate ASD‐risk genes (C Yuen et al, 2017). Table 1 summarizes clinical and genetic characteristics of all reported MED13 patients (including present patient).…”

“…MED13 gene pathogenic variants are linked to neurodevelopmental disorders with varying severity and course including intellectual disability (ID), autism spectrum disorder (ASD), and attention deficit disorder (ADHD) (De Nardi et al, 2021; Rogers et al, 2021; Snijders Blok et al, 2018). Very often patients also have delayed speech and language development.…”

Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies

“…Recently, de novo variants in the Mediator complex subunit 13 (MED13, OMIM 603,808) were detected in a cohort of 13 patients with intellectual disability and dysmorphisms [16]. Other features that were reported in patients with MED13 variants included optic nerve abnormalities, hearing loss, growth delay/restriction, hypotonia, mild congenital heart anomalies, epilepsy, and microcephaly [17][18][19][20].…”

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

“… 1 , 2 Although presumed that MED complex acts as a single unit, genetic defects of different subunits of the complex result in distinct disorders with overlapping clinical features, implying that either parts of the complex have separate functions or MED proteins have functions (outside of the complex) that are specific to each subunit. 2 , 3 , 4 , 5 , 6 , 7 Particularly, pathogenic (biallelic) variants in subunits part of the MED head module (eg, MED17 , OMIM 613668; MED20 , OMIM 612915; MED27 , OMIM 619286) have been implicated in rare neurologic disorders characterized by severe neurodevelopmental impairment, congenital and/or postnatal microcephaly, and variable degrees of progressive central nervous system (CNS) degeneration ( Supplementary Figure 1 ). 8 , 9 , 10 We hereby delineate a new autosomal recessive neurodegenerative disorder caused by a recurrent homozygous truncating variant in MED11 , encoding a subunit portion of the head module involved in the MED-complex stability.…”