A significant amount of research has been conducted on the over expression of the CTNNB1 gene and its connection to cancer. Researchers have published over 25,000 studies that have revealed the biology of the Wnt signaling pathway. 

However, very little research has been done on the gene as a result of a de novo mutation that results in too little beta catenin production. The underproduction of beta catenin causes CTNNB1 syndrome which our children are affected by. We have compiled some information from the following researchers on CTNNB1 gene mutation.

From the Lab of Dr. Michele Jacob

Alexander JM, Pirone A, Jacob MH. 2020. ”Excessive β-catenin in excitatory neurons results in reduced social and increased repetitive behaviors and altered expression of multiple genes linked to human autism.” Front. Synaptic Neurosci. 31;12:14.

CURE Infantile Spasms Consortium (Jacob MH) 2020. A team science approach to discover novel targets for infantile spasms (IS). Epilepsia Open  6(1):49-61.

Jacob, M. and Lentz, T.L. 1979.  “Localization of acetylcholine receptors by means of horseradish peroxidase-a-bungarotoxin during formation and development of the neuromuscular junction in the chick embryo.”  J. Cell Biol. 82:195-211.

Mohn JL*, Alexander J*, Pirone A, Palka C, Lee SY, Mebane L, Haydon P, Jacob MH.  2014.  “Adenomatous polyposis coli protein deletion leads to cognitive and autism-like disabilities.” *= co-first authors. Mol. Psychiatry 19:1133-42. PMID:24934177 (selected for Highlight- Mol. Psychiatry 19:1053.           

Pirone A*, Alexander JM*, Koenig JB, Cook-Snyder DR, Palnati M, Wickham RJ, Eden L, Shrestha N, Reijmers L, Biederer T, Miczek KA, Dulla CG, Jacob MH. 2018. “Social Stimulus Causes Aberrant  Activation of the Medial Prefrontal Cortex in a Mouse Model With Autism-Like Behaviors.”  Front Synaptic Neurosci. 10:35. PMID:30369876. *=co-first authors

Wickham R, Alexander J, Eden LW, Valencia-Yang M, Llamas J, Aubrey JR, Jacob MH. 2019. “Learning impairments and molecular changes in the brain caused by β-catenin loss.” Hum Mol Gen. 28:2965-2975. 

Additional Published Studies

Dubruc E, Putoux A, Labalme A, Rougeot C, Sanlaville D, Edery P. A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency. Am J Med Genet A. 2014 Jun;164A(6):1571-5. doi: 10.1002/ajmg.a.36484. Epub 2014 Mar 25.

Kharbanda M, Pilz DT, Tomkins S, Chandler K, Saggar A, Fryer A, McKay V, Louro P, Smith JC, Burn J, Kini U, De Burca A, FitzPatrick DR, Kinning E; DDD Study. Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals. Eur J Med Genet. 2017 Feb;60(2):130-135. doi: 10.1016/j.ejmg.2016.11.008. Epub 2016 Nov 30.

Jin, S.C., Lewis, S.A., Bakhtiari, S. et al. Mutations disrupting neuritogenesis genes confer risk for cerebral palsy. Nat Genet 52, 1046–1056 (2020).

Pipo-Deveza J, Fehlings D, Chitayat D, Yoon G, Sroka H, Tein I. Rationale for dopa-responsive CTNNB1/ß-catenin deficient dystonia. Mov Disord. 2018 Apr;33(4):656-657.

Rharass T, Lantow M, Gbankoto A, Weiss DG, Panáková D, Lucas S. Ascorbic acid alters cell fate commitment of human neural progenitors in a WNT/β-catenin/ROS signaling dependent manner. J Biomed Sci. 2017;24(1):78. Published 2017 Oct 16.

Wang H, Zhao Y, Yang L, Han S, Qi M. Identification of a novel splice mutation in CTNNB1 gene in a Chinese family with both severe intellectual disability and serious visual defects. Neurol Sci. 2019;40(8):1701-1704. 

Moreno-De-Luca A. et al. Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy. JAMA. 2021 Feb 2;325(5):467-475.

Ho SKL, Tsang MHY, Lee M, et al. CTNNB1 Neurodevelopmental Disorder. GeneReviews®. Seattle (WA): University of Washington, Seattle. 2022.

Miroševič Š, Khandelwal S, Sušjan P, Žakelj N, Gosar D, Forstnerič V, Lainšček D, Jerala R, Osredkar D. Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature. Int J Mol Sci. 2022 Oct 19;23(20):12564.

Srivastava S, Lewis SA, Cohen JS, et al. Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Cerebral Palsy: A Systematic Review and Meta-analysis. JAMA Neurol. 2022;79(12):1287–1295.

Kayumi, S., Pérez-Jurado, L. A., Corbett, M. A. et al. Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants. Genetics in Medicine. 2022;24(11):2351-2366.

Yan D, Sun Y, Xu N, Yu Y, Zhan Y; Mainland Chinese League of NEDSDV Rare Disease. Genetic and clinical characteristics of 24 mainland Chinese patients with CTNNB1 loss-of-function variants. Mol Genet Genomic Med. 2022 Nov;10(11):e2067.

Gonzalez-Mantilla PJ, Hu Y, Myers SM, et al. Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines: A Systematic Review and Meta-analysis. JAMA Pediatr. 2023 Mar 06.