ArticleAmerican journal of human genetics2013
An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin BCell reports. Medicine · 2022Pooled it
- From Thanatos to transcription: the emerging biology of THAP proteins.Cellular and molecular life sciences : CMLS · 2026Review
- Novel HCFC1 variants identified in patients with ASD/ADHD and previously unreported structural brain malformations reveal the potential for phenotypic expansion.Molecular genetics and metabolism reports · 2026Article
- Hcfc1 and Ogt Mediate Zebrafish CNS Regeneration Through Hippo/Yap Signalling.Cell proliferation · 2026Article
- Inherited disorders of cobalamin metabolism in childhood: biochemical and clinical perspectives.Frontiers in nutrition · 2026Review
- A Zebrafish Seizure Model of cblX Syndrome Reveals a Dose-Dependent Response to mTor Inhibition.Journal of developmental biology · 2025Article
- Animal models of methylmalonic acidemia: insights and challenges.Orphanet journal of rare diseases · 2025Review
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- HCF-1 as a key modulator of OGT function and O-GlcNAcylation in the liver.Scientific reports · 2025Article
- Epigenetic modifications in the murine liver upon depletion of transcriptional coregulator host cell factor 1.BMC genomics · 2025Article
- Improved biochemical and neurodevelopmental profiles with high-dose hydroxocobalamin therapy in cobalamin C defect.Journal of inherited metabolic disease · 2025Article
- Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.BMC medical genomics · 2024Article
- Dual rare genetic diseases in five pediatric patients: insights from next-generation diagnostic methods.Orphanet journal of rare diseases · 2024Article
- Genome-wide association identifies genomic regions influencing fillet color in Northwest Atlantic salmon (Frontiers in genetics · 2024Article
- Four Decades of Carrier Detection and Prenatal Diagnosis in Hemophilia A: Historical Overview, State of the Art and Future Directions.International journal of molecular sciences · 2023Review
- Overexpression ofAmerican journal of undergraduate research · 2023Article
- Article
- Abnormal chondrocyte intercalation in a zebrafish model ofbioRxiv : the preprint server for biology · 2023Article
- Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.Biomolecules · 2023Review
- Versatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.iScience · 2022Review
16 more citing papers are in PubMed but not listed here.
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18 authors.
Funding
Abstract
Derivatives of vitamin B12 (cobalamin) are essential cofactors for enzymes required in intermediary metabolism. Defects in cobalamin metabolism lead to disorders characterized by the accumulation of methylmalonic acid and/or homocysteine in blood and urine. The most common inborn error of cobalamin metabolism, combined methylmalonic acidemia and hyperhomocysteinemia, cblC type, is caused by mutations in MMACHC. However, several individuals with presumed cblC based on cellular and biochemical analysis do not have mutations in MMACHC. We used exome sequencing to identify the genetic basis of an X-linked form of combined methylmalonic acidemia and hyperhomocysteinemia, designated cblX. A missense mutation in a global transcriptional coregulator, HCFC1, was identified in the index case. Additional male subjects were ascertained through two international diagnostic laboratories, and 13/17 had one of five distinct missense mutations affecting three highly conserved amino acids within the HCFC1 kelch domain. A common phenotype of severe neurological symptoms including intractable epilepsy and profound neurocognitive impairment, along with variable biochemical manifestations, was observed in all affected subjects compared to individuals with early-onset cblC. The severe reduction in MMACHC mRNA and protein within subject fibroblast lines suggested a role for HCFC1 in transcriptional regulation of MMACHC, which was further supported by the identification of consensus HCFC1 binding sites in MMACHC. Furthermore, siRNA-mediated knockdown of HCFC1 expression resulted in the coordinate downregulation of MMACHC mRNA. This X-linked disorder demonstrates a distinct disease mechanism by which transcriptional dysregulation leads to an inborn error of metabolism with a complex clinical phenotype.
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