CAMTA1-related disorder: Phenotypic and molecular characterization of 26 new individuals and literature review

Al-Kateb H, Au PY, Berland S, Cogne B, Demurger F, Fluss J, Isidor B, Frank LM, Varvagiannis K, Koolen DA, McDonald M, Montgomery S, Moortgat S, Deprez M, Karadurmus D, Paulsen J, Reis A, Rieger M, Vasileiou G, Willing M, Shinawi M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Clinical Genetics Wiley-Blackwell

DOI: 10.1111/cge.14464

Abstract

Calmodulin-binding transcriptional activator 1 (CAMTA1) is highly expressed in the brain and plays a role in cell cycle regulation, cell differentiation, regulation of long-term memory, and initial development, maturation, and survival of cerebellar neurons. The existence of human neurological phenotypes, including cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA), associated with CAMTA1 variants, has further supported its role in brain functions. In this study, we phenotypically and molecularly characterize the largest cohort of individuals (n = 26) with 23 novel CAMTA1 variants (frameshift-7, nonsense-6, splicing-1, initiation codon-1, missense-5, and intragenic deletions-3) and compare the findings with all previously reported cases (total = 53). We show that the most notable phenotypic findings are developmental delay/intellectual disability, unsteady or uncoordinated gait, hypotonia, behavioral problems, and eye abnormalities. In addition, there is a high incidence of dysarthria, dysgraphia, microcephaly, gastrointestinal abnormalities, sleep difficulties, and nonspecific brain MRI findings; a few of which have been under-reported. More than one third of the variants in this cohort were inherited from an asymptomatic or mildly affected parent suggesting reduced penetrance and variable expressivity. Our cohort provides a comprehensive characterization of the spectrum of phenotypes and genotypes among individuals with CECBA and the large data will facilitate counseling and formulating management plans and surveillance recommendations for these individuals.

Authors with CRIS profile

André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Melissa Pauly Institute of Human Genetics Georgia Vasileiou Institute of Human Genetics

Involved external institutions

University of Calgary CA Canada (CA) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) CH Switzerland (CH) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Haukeland University Hospital / Haukeland universitetssykehus NO Norway (NO) Duke University Medical Center US United States (USA) (US) Mayo Clinic US United States (USA) (US) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) FR France (FR) Washington University US United States (USA) (US) Children's Hospital of The King's Daughters GB United Kingdom (GB)

How to cite

APA:

Al-Kateb, H., Au, P.Y., Berland, S., Cogne, B., Demurger, F., Fluss, J.,... Shinawi, M. (2023). CAMTA1-related disorder: Phenotypic and molecular characterization of 26 new individuals and literature review. Clinical Genetics. https://doi.org/10.1111/cge.14464

MLA:

Al-Kateb, Hussam, et al. "CAMTA1-related disorder: Phenotypic and molecular characterization of 26 new individuals and literature review." Clinical Genetics (2023).

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