ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
De novo variants in MED12 cause X-linked syndromic neurodevelopmental disorders in 18 females.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- A Novel Intronic Variant inGenes · 2026Review
- Thorough evaluation of a novel splice variant in a female patient with MED12-related intellectual disability.Neurogenetics · 2026Article
- Med13 is involved in the radial migration and contralateral projection of cortical neurons via PlxnA4.Communications biology · 2026Article
- Case Report: A novelFrontiers in psychiatry · 2026Article
- Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.Genes · 2025Review
- Antenatal Pulmonary Hypoplasia Expands the Variety of Phenotypes Associated With MED12-Related Disorders.Prenatal diagnosis · 2025Article
- Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts.European journal of human genetics : EJHG · 2025Article
- Functional characterization of the MED12 p.Arg1138Trp variant in females: implications for neural development and disease mechanism.Molecular medicine (Cambridge, Mass.) · 2025Article
- Review
- MED12 Loss-of-Function Variants as a Cause of Congenital Diaphragmatic Hernia in Females With Hardikar Syndrome and Nonspecific Intellectual Disability.American journal of medical genetics. Part A · 2025Article
- Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort.Human mutation · 2024Article
- Mutation spectrum of Kallmann syndrome: identification of five novel mutations across ANOS1 and FGFR1.Reproductive biology and endocrinology : RB&E · 2023Article
- Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.American journal of medical genetics. Part A · 2023Article
- Identification of genetic characteristics in pediatric epilepsy with focal cortical dysplasia type 2 using deep whole-exome sequencing.Molecular genetics & genomic medicine · 2022Article
- MED12-related Hardikar syndrome: Two additional cases and novel phenotypic features.American journal of medical genetics. Part A · 2022Article
- How can same-gene mutations promote both cancer and developmental disorders?Science advances · 2022Article
- Transcription Pause and Escape in Neurodevelopmental Disorders.Frontiers in neuroscience · 2022Review
- Correspondence on "De novo variants in MED12 cause X-linked syndromic neurodevelopmental disorders in 18 females" by Polla et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Response to Riccardi et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
32 authors at 12 institutions in 7 countries.
Funding
Abstract
purposeMED12 is a subunit of the Mediator multiprotein complex with a central role in RNA polymerase II transcription and regulation of cell growth, development, and differentiation. This might underlie the variable phenotypes in males carrying missense variants in MED12, including X-linked recessive Ohdo, Lujan, and FG syndromes.
methodsBy international matchmaking we assembled variant and clinical data on 18 females presenting with variable neurodevelopmental disorders (NDDs) and harboring de novo variants in MED12.
resultsFive nonsense variants clustered in the C-terminal region, two splice variants were found in the same exon 8 splice acceptor site, and 11 missense variants were distributed over the gene/protein. Protein truncating variants were associated with a severe, syndromic phenotype consisting of intellectual disability (ID), facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. De novo missense variants were associated with a less specific, but homogeneous phenotype including severe ID, autistic features, limited speech and variable other anomalies, overlapping both with females with truncating variants as well as males with missense variants.
conclusionWe establish de novo truncating variants in MED12 as causative for a distinct NDD and de novo missense variants as causative for a severe, less specific NDD in females.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.