Expanding the molecular spectrum and the neurological phenotype related to CAMTA1 variants.
CAMTA1
cerebellar dysfunction
clinical variation
developmental delay
genotype-phenotype correlations
intellectual disability
mutation spectrum
whole exome sequencing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
11
06
2020
revised:
18
10
2020
accepted:
28
10
2020
pubmed:
2
11
2020
medline:
24
11
2021
entrez:
1
11
2020
Statut:
ppublish
Résumé
The CAMTA1-associated phenotype was initially defined in patients with intragenic deletions and duplications who showed nonprogressive congenital ataxia, with or without intellectual disability. Here, we describe 10 individuals with CAMTA1 variants: nine previously unreported (likely) pathogenic variants comprising one missense, four frameshift and four nonsense variants, and one missense variant of unknown significance. Six patients were diagnosed following whole exome sequencing and four individuals with exome-based targeted panel analysis. Most of them present with developmental delay, manifesting in speech and motor delay. Other frequent findings are hypotonia, cognitive impairment, cerebellar dysfunction, oculomotor abnormalities, and behavioral problems. Feeding problems occur more frequently than previously observed. In addition, we present a systematic review of 19 previously published individuals with causal variants, including copy number, truncating, and missense variants. We note a tendency of more severe cognitive impairment and recurrent dysmorphic features in individuals with a copy number variant. Pathogenic variants are predominantly observed in and near the N- and C- terminal functional domains. Clinical heterogeneity is observed, but 3'-terminal variants seem to associate with less pronounced cerebellar dysfunction.
Substances chimiques
CAMTA1 protein, human
0
Calcium-Binding Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
259-268Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Finkler A, Ashery-Padan R, Fromm H. CAMTAs: calmodulin-binding transcription activators from plants to human. FEBS Lett. 2007;581(21):3893-3898. https://doi.org/10.1016/j.febslet.2007.07.051.
Kakar KU, Nawaz Z, Cui Z, et al. Evolutionary and expression analysis of CAMTA gene family in Nicotiana tabacum yielded insights into their origin, expansion and stress responses. Sci Rep. 2018;8(1):1-14. https://doi.org/10.1038/s41598-018-28148-9.
Han J, Gong P, Reddig K, Mitra M, Guo P, Li HS. The Fly CAMTA transcription factor potentiates deactivation of rhodopsin, a G protein-coupled light receptor. Cell. 2006;127(4):847-858. https://doi.org/10.1016/j.cell.2006.09.030.
Yang T, Poovaiah BW. A calmodulin-binding/CGCG box DNA-binding protein family involved in multiple signaling pathways in plants. J Biol Chem. 2002;277(47):45049-45058. https://doi.org/10.1074/jbc.M207941200.
Bouché N, Scharlat A, Snedden W, Bouchez D, Fromm H. A novel family of calmodulin-binding transcription activators in multicellular organisms. J Biol Chem. 2002;277(24):21851-21861. https://doi.org/10.1074/jbc.M200268200.
Song K, Backs J, McAnally J, et al. The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases. Cell. 2006;125(3):453-466. https://doi.org/10.1016/j.cell.2006.02.048.
Henrich KO, Bauer T, Schulte J, et al. CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells. Cancer Res. 2011;71(8):3142-3151. https://doi.org/10.1158/0008-5472.CAN-10-3014.
Schraivogel D, Weinmann L, Beier D, et al. CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells. EMBO J. 2011;30(20):4309-4322. https://doi.org/10.1038/emboj.2011.301.
Nakatani K, Nishioka J, Itakura T, et al. Cell cycle-dependent transcriptional regulation of calmodulin-binding transcription activator 1 in neuroblastoma cells. Int J Oncol. 2004;24(6):1407-1412. https://doi.org/10.3892/ijo.24.6.1407.
Kim MY, Yim SH, Kwon MS, et al. Recurrent genomic alterations with impact on survival in colorectal cancer identified by genome-wide array comparative genomic hybridization. Gastroenterology. 2006;131(6):1913-1924. https://doi.org/10.1053/j.gastro.2006.10.021.
Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M. Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene. Clin Cancer Res. 2005;11(3):1119-1128.
Huentelman MJ, Papassotiropoulos A, Craig DW, et al. Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance. Hum Mol Genet. 2007;16(12):1469-1477. https://doi.org/10.1093/hmg/ddm097.
Bas-Orth C, Tan YW, Oliveira AMM, Bengtson CP, Bading H. The calmodulin-binding transcription activator CAMTA1 is required for long-term memory formation in mice. Learn Mem. 2016;23(6):313-321. https://doi.org/10.1101/lm.041111.115.
Miller LA, Gunstad J, Spitznagel MB, et al. CAMTA1 T polymorphism is associated with neuropsychological test performance in older adults with cardiovascular disease. Psychogeriatrics. 2011;11(3):135-140. https://doi.org/10.1111/j.1479-8301.2011.00357.x.
Long C, Grueter CE, Song K, et al. Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor. Proc Natl Acad Sci U S A. 2014;111(31):11521-11526. https://doi.org/10.1073/pnas.1411251111.
Thevenon J, Lopez E, Keren B, et al. Intragenic CAMTA1 rearrangements cause non-progressive congenital ataxia with or without intellectual disability. J Med Genet. 2012;49(6):400-408. https://doi.org/10.1136/jmedgenet-2012-100856.
Shinawi M, Coorg R, Shimony JS, Grange DK, Al-Kateb H. Intragenic CAMTA1 deletions are associated with a spectrum of neurobehavioral phenotypes. Clin Genet. 2015;87(5):478-482. https://doi.org/10.1111/cge.12407.
Fitzgerald TW, Gerety SS, Jones WD, et al. Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015;519(7542):223-228. https://doi.org/10.1038/nature14135.
Agarwal S, Gilbert R, Lau HA. Novel nonsense Calmodulin-binding transcription activator 1 mutation presenting as a tremor-predominant phenotype. Mov Disord Clin Pract. 2016;3(6):611-614. https://doi.org/10.1002/mdc3.12328.
Wijnen IGM, Veenstra-Knol HE, Vansenne F, et al. De novo variants in CAMTA1 cause a syndrome variably associated with spasticity, ataxia, and intellectual disability. Eur J Hum Genet. 2020;28:763-769. https://doi.org/10.1038/s41431-020-0600-5.
Chérot E, Keren B, Dubourg C, et al. Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of 2 clinical units and 216 patients. Clin Genet. 2018;93(3):567-576. https://doi.org/10.1111/cge.13102.
Callaghan DB, Rogic S, Tan PPC, et al. Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort. Clin Genet. 2019;96(3):199-206. https://doi.org/10.1111/cge.13556.
Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36(10):928-930. https://doi.org/10.1002/humu.22844.
Firth HV, Richards SM, Bevan AP, et al. DECIPHER: database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am J Hum Genet. 2009;84(4):524-533. https://doi.org/10.1016/j.ajhg.2009.03.010.
Basu SN, Kollu R, Banerjee-Basu S. AutDB: a gene reference resource for autism research. Nucleic Acids Res. 2009;37(suppl 1):D832-D836. https://doi.org/10.1093/nar/gkn835.
Retterer K, Juusola J, Cho MT, et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2016;18(7):696-704. https://doi.org/10.1038/gim.2015.148.
Wright CF, Fitzgerald TW, Jones WD, et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet. 2015;385(9975):1305-1314. https://doi.org/10.1016/S0140-6736(14)61705-0.
Ramu A, Noordam MJ, Schwartz RS, et al. DeNovoGear: De novo indel and point mutation discovery and phasing. Nat Methods. 2013;10(10):985-987. https://doi.org/10.1038/nmeth.2611.
Wang J, Al-Ouran R, Hu Y, et al. MARRVEL: integration of human and model organism genetic resources to facilitate functional annotation of the human genome. Am J Hum Genet. 2017;100(6):843-853. https://doi.org/10.1016/j.ajhg.2017.04.010.
Mikhail FM, Lose EJ, Robin NH, et al. Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders. Am J Med Genet Part A. 2011;155(10):2386-2396. https://doi.org/10.1002/ajmg.a.34177.
Redin C, Brand H, Collins RL, et al. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Nat Genet. 2017;49(1):36-45. https://doi.org/10.1038/ng.3720.
Coci EG, Koehler U, Liehr T, et al. CANPMR syndrome and chromosome 1p32-p31 deletion syndrome coexist in two related individuals affected by simultaneous haplo-insufficiency of CAMTA1 and NIFA genes. Mol Cytogenet. 2016;9(1):10. https://doi.org/10.1186/s13039-016-0219-y.
Nicita F, Nardella M, Bellacchio E, et al. Heterozygous missense variants of SPTBN2 are a frequent cause of congenital cerebellar ataxia. Clin Genet. 2019;96(2):169-175. https://doi.org/10.1111/cge.13562.
Zambonin JL, Bellomo A, Ben-Pazi H, et al. Spinocerebellar ataxia type 29 due to mutations in ITPR1: a case series and review of this emerging congenital ataxia. Orphanet J Rare Dis. 2017;12(1):121. https://doi.org/10.1186/s13023-017-0672-7.
Izquierdo-Serra M, Fernández-Fernández JM, Serrano M. Rare CACNA1A mutations leading to congenital ataxia. Pflugers Arch Eur J Physiol. 2020;472(7):791-809. https://doi.org/10.1007/s00424-020-02396-z.
Gong P, Han J, Reddig K, Li HS. A potential dimerization region of dCAMTA is critical for termination of fly visual response. J Biol Chem. 2007;282(29):21253-21258. https://doi.org/10.1074/jbc.M701223200.
Liu W, Xie Y, Ma J, et al. IBS: an illustrator for the presentation and visualization of biological sequences. Bioinformatics. 2015;31(20):3359-3361. https://doi.org/10.1093/bioinformatics/btv362.