A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency
- PMID: 24668549
- DOI: 10.1002/ajmg.a.36484
A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency
Abstract
A girl patient born to healthy nonconsanguineous parents was referred at age 3 years and 2 months to our genetics department for testing due to developmental delay and postnatal microcephaly. Initial clinical evaluation revealed an overall developmental delay, mildly dysmorphic features, thin, sparse fair hair, and fair skin. Postnatal microcephaly and progressive ataxia and spasticity appeared later. Array CGH karyotyping showed a 333 kb de novo microdeletion on 3p22 covering the entire genomic sequence of a single gene, CTNNB1, which codes for β-catenin. β-catenin is a sub-unit of a multiprotein complex, which is part of the Wnt signaling pathway. In mice, a conditional homozygous β-catenin knockout displays loss of neurons, impaired craniofacial development, and hair follicle defects, which is similar to the phenotype presented by the patient described in this clinical report. Thus, CTNNB1 haploinsufficiency causes neuronal loss, craniofacial anomalies and hair follicle defects in both humans and mice. Point mutations in CTNNB1 in human have recently been reported but this is the first observation of a new recognizable multiple congenital anomaly/mental retardation syndrome caused by CTNNB1 haploinsufficiency. This clinical report should prompt a search for point mutations in CTNNB1 in patients presenting developmental delay, mild hair, skin and facial anomalies, and neurodegeneration characterized by postnatal microcephaly, and progressive ataxia and spasticity. © 2014 Wiley Periodicals, Inc.
Keywords: CTNNB1 gene; developmental delay; fair hair; haploinsufficiency; mild dysmorphic features; postnatal microcephaly; progressive ataxia; progressive spasticity; sparse.
© 2014 Wiley Periodicals, Inc.
Similar articles
-
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). 2017 May;96(20):e6914. doi: 10.1097/MD.0000000000006914. Medicine (Baltimore). 2017. PMID: 28514307 Free PMC article. Review.
-
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. Eur J Med Genet. 2017. PMID: 27915094 Free PMC article.
-
De novo mutations in beta-catenin (CTNNB1) appear to be a frequent cause of intellectual disability: expanding the mutational and clinical spectrum.Hum Genet. 2015 Jan;134(1):97-109. doi: 10.1007/s00439-014-1498-1. Epub 2014 Oct 19. Hum Genet. 2015. PMID: 25326669
-
A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report.BMC Neurol. 2016 Mar 12;16:35. doi: 10.1186/s12883-016-0554-y. BMC Neurol. 2016. PMID: 26968164 Free PMC article.
-
Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature.BMC Med Genet. 2016 Feb 27;17:15. doi: 10.1186/s12881-016-0276-4. BMC Med Genet. 2016. PMID: 26922654 Free PMC article. Review.
Cited by
-
Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature.Int J Mol Sci. 2022 Oct 19;23(20):12564. doi: 10.3390/ijms232012564. Int J Mol Sci. 2022. PMID: 36293418 Free PMC article. Review.
-
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 Aug;40(8):1701-1704. doi: 10.1007/s10072-019-03823-5. Epub 2019 Mar 30. Neurol Sci. 2019. PMID: 30929091 Free PMC article.
-
The extended clinical and genetic spectrum of CTNNB1-related neurodevelopmental disorder.Front Pediatr. 2022 Jul 22;10:960450. doi: 10.3389/fped.2022.960450. eCollection 2022. Front Pediatr. 2022. PMID: 35935366 Free PMC article.
-
Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk.J Neurodev Disord. 2019 Jun 15;11(1):10. doi: 10.1186/s11689-019-9268-y. J Neurodev Disord. 2019. PMID: 31202261 Free PMC article. Review.
-
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). 2017 May;96(20):e6914. doi: 10.1097/MD.0000000000006914. Medicine (Baltimore). 2017. PMID: 28514307 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous
