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Of the 22 genes that had high-impact variants filtered through stringent bioinformatic approaches in at least three dyslexia cases, five genes were validated in the follow-up analysis:\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    ,\n                    <jats:italic>CACNA1G<\/jats:italic>\n                    ,\n                    <jats:italic>CLDN3<\/jats:italic>\n                    ,\n                    <jats:italic>CNGB1<\/jats:italic>\n                    , and\n                    <jats:italic>CP<\/jats:italic>\n                    . Notably, a specific variant (7-73769649-G-A; c.C401T; p.P134L) in the\n                    <jats:italic>CLDN3<\/jats:italic>\n                    gene was identified in six independent cases, showing a four-fold higher frequency compared to population reference datasets.\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    and\n                    <jats:italic>CACNA1G<\/jats:italic>\n                    encode subunits of voltage-gated calcium channels expressed in neurons, and variants in both genes have been implicated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and epilepsy. Segregation analyses in available family members were consistent with patterns of dominant inheritance with variable expressivity. In total, high-impact variants in the five genes of interest were found in 26% (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200914) of individuals of the discovery cohort. Overall, our findings support the involvement of rare variants in developmental dyslexia and indicate that larger WES studies may uncover additional associated genes.\n                  <\/jats:p>","DOI":"10.1007\/s00439-025-02796-0","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:35:13Z","timestamp":1766576113000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole-exome sequencing in children with dyslexia implicates rare variants in CLDN3 and ion channel genes"],"prefix":"10.1007","volume":"145","author":[{"given":"Krzysztof","family":"Marianski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel B.","family":"Talcott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P.","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon E.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy V.M.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne F.","family":"Newbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Paracchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"2796_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoc.2020.100780","volume":"19","author":"AA Alshamrani","year":"2020","unstructured":"Alshamrani AA, Raddadi O, Schatz P et al (2020) Severe retinitis pigmentosa phenotype associated with novel CNGB1 variants. 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