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. 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.

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

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. *=co-first authors

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.

Jacob M, Lentz TL. 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.

Additional Publications

Sinibaldi L, Garone G, Mandarino A, Iarossi G, Chioma L, Dentici M, Merla G, Agolini E, Micalizzi A, Calcagni G et al. 2023. Congenital heart defects in CTNNB1 syndrome: Raising clinical awareness. Clin Genet.

Gonzalez-Mantilla PJ, Hu Y, Myers SM, Finucane BM, Ledbetter DH, Martin CL, Moreno-De-Luca A. 2023. Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines: A Systematic Review and Meta-analysis. JAMA Pediatr. 177(5):472-478. 

Wenting Z, Tong Y, Wei W, Weihong S, Tao T. 2023. CTNNB1 in Neurodevelopmental Disorders. Front. Psychiatry. 14.

Lee S, Jang SS, Park S, Yoon JG, Kim SY, Lim BC, Chae JH. 2022. The extended clinical and genetic spectrum of CTNNB1-related neurodevelopmental disorder. Front Pediatr. 10:960450.

Ho SKL, Tsang MHY, Lee M, Cheng SSW, Luk H-M, Lo IFM, Chung BHY. 2022. CTNNB1 Neurodevelopmental Disorder. GeneReviews® [Internet]. University of Washington, Seattle. 

Dashti S, Salehpour S, Ghasemi MR, Sadeghi H, Rostami M, Hashemi-Gorji F, Mirfakhraie R, Yassaee VR, Miryounesi M. 2022. Identification of a novel de novo mutation in the CTNNB1 gene in an Iranian patient with intellectual disability. Neurol Sci. 43(4):2859-2863.

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

Srivastava S, Lewis SA, Cohen JS, Zhang B, Aravamuthan BR, Chopra M, Sahin M, Kruer MC, Poduri A. 2022. Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Cerebral Palsy: A Systematic Review and Meta-analysis. JAMA Neurol. 79(12):1287–1295. 

Kayumi S, Pérez-Jurado LA, Palomares M, Rangu S, Sheppard SE, Chung WK, Kruer MC, Kharbanda M, Amor DJ, Corbett MA et al. 2022. Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants. Genet Med. 24(11):2351-2366. 

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

Taylor RL, Soriano CS, Williams S, Dzulova D, Ashworth J, Hall G, Gale T, Lloyd IC, Inglehearn CF, Toomes C et al. 2022. Bi-allelic mutation of CTNNB1 causes a severe form of syndromic microphthalmia, persistent foetal vasculature and vitreoretinal dysplasia. Orphanet J Rare Dis. 17(1):110.

Ho S, Tsang MH, Fung JL, Huang H, Chow CB, Cheng SS, Luk HM, Chung BH, Lo IF. 2022. CTNNB1-related neurodevelopmental disorder in a Chinese population: A case series. Am J Med Genet A. 188(1):130-137.

Moreno-De-Luca A, Millan F, Pesacreta DR, Elloumi HZ, Oetjens MT, Teigen C, Wain KE, Scuffins J, Myers SM, Torene RI, et al. 2021. Molecular diagnostic yield of exome sequencing in patients with cerebral palsy. JAMA. 325(5):467. 

Rossetti LZ, Bekheirnia MR, Lewis AM, Mefford HC, Golden-Grant K, Tarczy-Hornoch K, Briere LC, Sweetser DA, Walker MA, Wangler MF et al. 2021. Missense variants in CTNNB1 can be associated with vitreoretinopathy-Seven new cases of CTNNB1-associated neurodevelopmental disorder including a previously unreported retinal phenotype. Mol Genet Genomic Med. 9(1):e1542.

Ke Z, Chen Y. 2020. Case Report: A de novo CTNNB1 Nonsense Mutation Associated With Neurodevelopmental Disorder, Retinal Detachment, Polydactyly. Front Pediatr. 8:575673.

Jin SC, Lewis SA, Bakhtiari S, Zeng X, Sierant MC, Shetty S, Nordlie SM, Elie A, Corbett MA, Norton BY, et al. 2020. Mutations disrupting neuritogenesis genes confer risk for cerebral palsy. Nat Genet. 52(10):1046–1056. 

Coussa RG, Zhao Y, DeBenedictis MJ, Babiuch A, Sears J, Traboulsi EI. 2020. Novel mutation in CTNNB1 causes familial exudative vitreoretinopathy (FEVR) and microcephaly: case report and review of the literature. Ophthalmic Genet. 41(1):63-68.

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

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

Li N, Xu Y, Li G, Yu T, Yao RE, Wang X, Wang J. 2017. Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly presented with retinal detachment, lens and vitreous opacities, microcephaly, and developmental delay: Case report and literature review. Medicine (Baltimore). 96(20):e6914.

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. 2017. Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals. Eur J Med Gen. 60(2):130–135. 

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

Dubruc E, Putoux A, Labalme A, Rougeot C, Sanlaville D, Edery P. 2014. A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency. Am J Med Genet A. 164(6):1571–1575.