Chromosome alignment-maintaining phosphoprotein 1 (CHAMP1) also known as zinc finger protein 828 (ZNF828) is a protein that in humans is encoded by the CHAMP1 gene.[5] CHAMP1 is a key component of a protein complex that has a role in facilitating homology-directed repair of DNA.[6]
Clinical Significance
Mutations in the CHAMP1 gene are associated with a neurodevelopmental disorder characterized by intellectual disability and severe speech impairment.[7][8] This condition, often referred to as CHAMP1-related neurodevelopmental disorder, arises from a pathogenic variant in one of the two copies of the gene.[9] The majority of cases result from de novo mutations, meaning they are not inherited from the parents.[10]
Individuals with this disorder typically present with a range of symptoms, including global developmental delay, intellectual disability, and significant speech impairment.[11][12] Common behavioral issues include features consistent with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).[13] Other frequently reported conditions include feeding difficulties, vision problems, seizures, and hypotonia (low muscle tone).[11]
Diagnosis is confirmed through genetic testing. Management is supportive and tailored to the individual's symptoms, involving physical, occupational, and speech therapies, as well as educational support.[12]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000198824 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047710 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: C13orf8 chromosome 13 open reading frame 8".
- ^ Li F, Zhang T, Syed A, Elbakry A, Holmer N, Nguyen H, Mukkavalli S, Greenberg RA, D'Andrea AD (February 2025). "CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair". Nat Commun. 16 (1) 1714. Bibcode:2025NatCo..16.1714L. doi:10.1038/s41467-025-56834-6. PMC 11832927. PMID 39962076.
- ^ Hempel M, Cremer K, Ockeloen CW (November 2015). "De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment". Journal of Medical Genetics. 52 (11): 758–762. doi:10.1177/1545968315604395. PMC 4680190. PMID 26359341.
- ^ Héron D, Tabet AC, Mignot C (October 2018). "De Novo Truncating Mutations in the Kinetore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability". The American Journal of Human Genetics. 103 (4): 603–611. doi:10.1016/j.ajhg.2018.08.011. PMC 6174321. PMID 30196985.
- ^ Mattioli F, Magini P, Bedeschi MF (April 2024). "CHAMP1-related disorders: pathomechanisms triggered by different genomic alterations define distinct nosological categories". Human Genetics. 31 (21): 30836–30848. doi:10.1007/s11356-024-33168-2. PMC 11096217. PMID 38622415.
- ^ Tanaka AJ, Cho MT, Millan F (December 2018). "De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features". Human Mutation. 39 (12): 1903–1915. doi:10.1002/humu.23652. PMC 6294708. PMID 30252159.
- ^ a b Schaaf CP, Koster J, Foulds N (May 2023). "A disease conceptual model for CHAMP1-related disorder". Journal of Neurodevelopmental Disorders. 15 (1): 19. doi:10.1186/s12941-023-00586-y. PMC 10202970. PMID 37202758.
- ^ a b Abi Raad S, Salignat V, Auvin S (July 2023). "CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature". Genes. 14 (7): 7361–7374. doi:10.3390/genes14071432. PMC 10381650. PMID 37489569.
- ^ Levy T, Le Caignec C, Isidor B (July 2022). "CHAMP1 disorder is associated with a complex neurobehavioral phenotype including autism, ADHD, repetitive behaviors and sensory symptoms". Human Molecular Genetics. 31 (15): 2582–2594. doi:10.1093/hmg/ddac018. PMC 9288764. PMID 35084013.
External links
Further reading
- Yan H, Wang Y, Wang J (January 2023). "Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene". Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 40 (1): 58–61. doi:10.1186/s40001-022-00978-4. PMC 9827673. PMID 36624515.
- Wang MM, Peng J, Zhou Y, He XY, Cao B (October 2020). "Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report". Zhongguo Dang Dai Er Ke Za Zhi. 22 (10): 1081–1084. doi:10.1186/s13195-020-00686-3. PMC 7572235. PMID 33066807.
- Itoh G, Kaji M, Kito K, Kabe Y, Hata A, Kiyono T (January 2011). "CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment". The EMBO Journal. 30 (1): 130–44. doi:10.1038/emboj.2010.286. PMC 3018590. PMID 21081896.
- Li F, Zhang T, Syed A, Elbakry A, Holmer N, Nguyen H, Mukkavalli S, Greenberg RA, D'Andrea AD (September 2022). "CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair". Cell Reports. 40 (10) 111297. doi:10.1016/j.celrep.2022.111297. PMC 9481717. PMID 36070669.
- Ben-Haim R, Zehavi Y, Yilmaz R, Sagi-Dain L, Ben-Zeev B, Tzadok M (October 2019). "CHAMP1 Mutations cause Refractory Infantile Myoclonic Epilepsy". Journal of Pediatric Neurology. 17 (4): 153–157. doi:10.1055/s-0039-1693158.
- Fujita H, Fukuda T, Hori M, Nakagawa K (May 2022). "CHAMP1-POGZ counteracts the inhibitory effect of 53BP1 on homologous recombination and affects PARP inhibitor resistance". Oncogene. 41 (19): 2706–2718. doi:10.1038/s41388-022-02299-6. PMC 9007991. PMID 35437340.
Deciphering Developmental Disorders Study (March 2015). "Large-scale discovery of novel genetic causes of developmental disorders". Nature. 519 (7542): 223–8. Bibcode:2015Natur.519..223T. doi:10.1038/nature14135. PMC 5955210. PMID 25533962.
- Whelan, C; Clegg, T (2020). "Language in CHAMP1 Syndrome". CHAMP1 Research Foundation.
- Clegg, T; Glaser, K (2020). "Neurodevelopmental Phenotypes in Individuals with Pathogenic Variants in CHAMP1". CHAMP1 Research Foundation.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.