ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
De novo loss-of-function variants in X-linked MED12 are associated with Hardikar syndrome in 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 20 papers.
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Who cites it
20 citing papers in PubMed, 33 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
- 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
- MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mediator complex: update of key insights into transcriptional regulation of ancestral framework and its role in cardiovascular diseases.European journal of medical research · 2025Review
- Approaches to Evaluate Whole Exome Sequencing Data That Incorporate Genetic Intolerance Scores for Congenital Anomalies, Including Intronic Regions Adjacent to Exons.Molecular genetics & genomic medicine · 2025Article
- 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
- Syndromic variants of biliary atresia.World journal of pediatric surgery · 2025Review
- Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies.BMC medical genomics · 2024Article
- Skewed X-chromosome inactivation in unsolved neurodevelopmental disease cases can guide re-evaluation For X-linked genes.European journal of human genetics : EJHG · 2023Article
- A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature.American journal of medical genetics. Part A · 2023Article
- MED12-related Hardikar syndrome: Two additional cases and novel phenotypic features.American journal of medical genetics. Part A · 2022Article
- Transcription Pause and Escape in Neurodevelopmental Disorders.Frontiers in neuroscience · 2022Review
- A novel nonsense variant inClinical case reports · 2021Article
- 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
- Article
- The Impact of X-Chromosome Inactivation on Phenotypic Expression of X-Linked Neurodevelopmental Disorders.Brain sciences · 2021Review
- Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeHardikar syndrome (MIM 612726) is a rare multiple congenital anomaly syndrome characterized by facial clefting, pigmentary retinopathy, biliary anomalies, and intestinal malrotation, but with preserved cognition. Only four patients have been reported previously, and none had a molecular diagnosis. Our objective was to identify the genetic basis of Hardikar syndrome (HS) and expand the phenotypic spectrum of this disorder.
methodsWe performed exome sequencing on two previously reported and five unpublished female patients with a clinical diagnosis of HS. X-chromosome inactivation (XCI) studies were also performed.
resultsWe report clinical features of HS with previously undescribed phenotypes, including a fatal unprovoked intracranial hemorrhage at age 21. We additionally report the discovery of de novo pathogenic nonsense and frameshift variants in MED12 in these seven individuals and evidence of extremely skewed XCI in all patients with informative testing.
conclusionPathogenic missense variants in the X-chromosome gene MED12 have previously been associated with Opitz-Kaveggia syndrome, Lujan syndrome, Ohdo syndrome, and nonsyndromic intellectual disability, primarily in males. We propose a fifth, female-specific phenotype for MED12, and suggest that nonsense and frameshift loss-of-function MED12 variants in females cause HS. This expands the MED12-associated phenotype in females beyond intellectual disability.
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