{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:06Z","timestamp":1753869726237,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>AHNAK2<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we report a female 24\u2010year\u2010old patient diagnosed with a cardio\u2010facio\u2010cutaneous\u2010like phenotype (CFC\u2010like), 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 <jats:italic>AHNAK2<\/jats:italic> gene detected by exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This patient had no detectable variant in any of the genes known to be associated with the cardio\u2010facio\u2010cutaneous 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We discuss an alternative interpretation on the potential involvement of the two missense mutations in the <jats:italic>AHNAK2<\/jats:italic> gene on the expression of CFC\u2010like phenotype in this patient based on inter\u2010allelic complementation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2012","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T08:33:22Z","timestamp":1657010002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exome sequencing in a child with neurodevelopmental disorder and epilepsy: Variant analysis of the <scp>AHNAK2<\/scp> gene"],"prefix":"10.1002","volume":"10","author":[{"given":"Mirella","family":"Vinci","sequence":"first","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petri","family":"Kursula","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Bergen Norway"},{"name":"Biocenter Oulu &amp; Faculty of Biochemistry and Molecular Medicine University of Oulu  Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Greco","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Elia","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0121-3396","authenticated-orcid":false,"given":"Luigi","family":"Vetri","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelo","family":"Schepis","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Chiavetta","sequence":"additional","affiliation":[{"name":"Oasi Research Institute\u2010IRCCS  Troina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Donadio","sequence":"additional","affiliation":[{"name":"Department of Sciences for Health Promotion and Mother and Child Care \u201cG. 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