Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder

Albuainain F, Shi Y, Lor-Zade S, Hüffmeier U, Pauly M, Reis A, Faivre L, Maraval J, Bruel AL, Them FTM, Haack TB, Grasshoff U, Horber V, Schot R, van Slegtenhorst M, Wilke M, Barakat TS (2024)

Publication Type: Journal article

Publication year: 2024

Journal

European Journal of Human Genetics Nature Publishing Group: Open Access Hybrid Model Option B

DOI: 10.1038/s41431-023-01530-6

Abstract

Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.

Authors with CRIS profile

Ulrike Hüffmeier Lehrstuhl für Humangenetik Melissa Pauly Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik

Involved external institutions

Universitätsklinikum Tübingen DE Germany (DE) Erasmus University Medical Center (MC) NL Netherlands (NL) Eberhard Karls Universität Tübingen DE Germany (DE) Centre hospitalier universitaire (CHU) de Dijon Bourgogne FR France (FR) Université de Bourgogne (uB) / University of Burgundy / University of Dijon FR France (FR)

How to cite

APA:

Albuainain, F., Shi, Y., Lor-Zade, S., Hüffmeier, U., Pauly, M., Reis, A.,... Barakat, T.S. (2024). Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder. European Journal of Human Genetics. https://dx.doi.org/10.1038/s41431-023-01530-6

MLA:

Albuainain, Fatimah, et al. "Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder." European Journal of Human Genetics (2024).

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