University of Oulu

Vinci, M., Kursula, P., Greco, D., Elia, M., Vetri, L., Schepis, C., Chiavetta, V., Donadio, S., Roccella, M., Carotenuto, M., Romano, V., & Calì, F. (2022). Exome sequencing in a child with neurodevelopmental disorder and epilepsy: Variant analysis of the AHNAK2 gene. Molecular Genetics & Genomic Medicine, 10(9).

Exome sequencing in a child with neurodevelopmental disorder and epilepsy : variant analysis of the AHNAK2 gene

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Author: Vinci, Mirella1; Kursula, Petri2,3; Greco, Donatella1;
Organizations: 1Oasi Research Institute-IRCCS, Troina, Italy
2Department of Biomedicine, University of Bergen, Bergen, Norway
3Biocenter Oulu & Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
4Department of Sciences for Health Promotion and Mother and Child Care “G. D'Alessandro”, University of Palermo, Palermo, Italy
5Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo, Italy
6Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-03-15


Background/Objectives: The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking.

Methods: Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing.

Results: This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions.

Conclusions: We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation.

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Series: Molecular genetics & genomic medicine
ISSN: 2324-9269
ISSN-E: 2324-9269
ISSN-L: 2324-9269
Volume: 10
Issue: 9
Article number: e2012
DOI: 10.1002/mgg3.2012
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
Funding: This work was partially supported by the Italian Ministry of Health – Ricerca Corrente - and ‘5 per mille’ funding.
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.