{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:46Z","timestamp":1792790446624,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,4]]},"group-title":"Genetics","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health","award":["1R03DC010886-01A1"],"award-info":[{"award-number":["1R03DC010886-01A1"]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Speech-Language-Hearing Foundation New Century Scholars Doctoral Scholarship","id":[{"id":"https:\/\/ror.org\/03wjf5d60","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Childhood apraxia of speech (CAS) is a neurodevelopmental disorder of speech-motor planning and programming, associated with literacy, academic, and psychosocial difficulties. We performed whole-exome sequencing in 11 families comprising 21 affected and 15 unaffected individuals with phenotyping spanning speech, language, cognition, literacy, and motor function. We identified 60 prioritized variant observations representing 22 unique variants across 20 genes with family-based segregation analysis assessed in informative relatives; 5 arose\n                  <jats:italic>de novo<\/jats:italic>\n                  . Our cohort included multiple affected siblings and extended relatives, with several families carrying multiple prioritized variants, suggesting cumulative or oligogenic susceptibility. Speech and literacy impairment co-occurred with oral-motor, feeding, and fine-motor difficulties. BrainSpan co-expression analysis identified\n                  <jats:italic>MECP2<\/jats:italic>\n                  and\n                  <jats:italic>ANK2<\/jats:italic>\n                  as the genes with the highest observed connectivity in the sampled postnatal network. Exploratory analysis of the KOLF2.1J perturbation atlas in undifferentiated human induced pluripotent stem cells identified a positive\n                  <jats:italic>LMO3<\/jats:italic>\n                  expression-response score following\n                  <jats:italic>NIPBL<\/jats:italic>\n                  repression and opposing\n                  <jats:italic>LMO3<\/jats:italic>\n                  and\n                  <jats:italic>ANK2<\/jats:italic>\n                  response directions within a cohesin-associated perturbation cluster. These observations motivate testing in human neural cells. Functional enrichment, protein-association, and developmental-expression analyses supported shared biological themes involving chromatin regulation, neuronal signaling, and extracellular-matrix organization. Among six families, multiple affected relatives shared prioritized variants across a unique set of several genes, demonstrating multilocus candidate profiles whose individual and combined effects may contribute to CAS susceptibility. We propose four novel CAS candidate genes\u2014\n                  <jats:italic>LMO3<\/jats:italic>\n                  and\n                  <jats:italic>PCDH10<\/jats:italic>\n                  , previously linked to human accelerated regions, as well as\n                  <jats:italic>MYCBP2<\/jats:italic>\n                  and\n                  <jats:italic>PTPRS<\/jats:italic>\n                  . Our work provides multiple testable hypotheses for future variant-specific functional validation in speech-motor development.\n                <\/jats:p>","DOI":"10.64898\/2026.10.03.756424","type":"posted-content","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:05:21Z","timestamp":1791187521000},"source":"Crossref","is-referenced-by-count":0,"title":["Developmental Convergence Across Diverse Genetic Architectures in Childhood Apraxia of Speech"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3816-8523","authenticated-orcid":false,"given":"Tiffanie","family":"White","sequence":"first","affiliation":[{"name":"Krieger School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8938-2773","authenticated-orcid":false,"given":"Marjan","family":"Chapi","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-3630","authenticated-orcid":false,"given":"Caitlin","family":"Raaz","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, University of Northern Colorado, Greeley, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9620-3157","authenticated-orcid":false,"given":"Laurel","family":"Bruce","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8405-5945","authenticated-orcid":false,"given":"Akshit","family":"Modi","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6192-7836","authenticated-orcid":false,"given":"Valentin","family":"Dinu","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-7497","authenticated-orcid":false,"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-6828","authenticated-orcid":false,"given":"Judith","family":"Klein-Seetharaman","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-8522","authenticated-orcid":false,"given":"Beate","family":"Peter","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100803500452000_2026.10.03.756424v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00872-y"},{"key":"2026100803500452000_2026.10.03.756424v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06145"},{"key":"2026100803500452000_2026.10.03.756424v1.3","unstructured":"American Speech-Language-Hearing Association (n.d.) 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