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Functional bioenergetic assessments showed no significant mitochondrial respiratory defects, and riboflavin (Rf) status evaluation excluded a deficiency in Rf transporters as a cause of hearing loss. Clinical findings were consistent with Kilquist syndrome (KILQS), and genetic investigations confirmed the diagnosis by identifying a novel homozygous splice\u2010site variant, c.[3101\u20101G&gt;C];[3101\u20101G&gt;C], in the\n                    <jats:italic>SLC12A2<\/jats:italic>\n                    gene, which encodes the Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010K\n                    <jats:sup>+<\/jats:sup>\n                    \u20102Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    Cotransporter 1 (NKCC1) protein. The effect of this mutation was further investigated using exon\u2010walking PCR and Sanger sequencing, which confirmed exon 23 skipping in the patient's mRNA, resulting in a truncated NKCC1 protein.\n                    <jats:italic>In silico<\/jats:italic>\n                    structural modeling suggested compromised dimerization stability, which was supported by immunoblotting analysis, revealing the absence of the dimeric form of NKCC1 in patient\u2010derived peripheral blood mononuclear cells. This study provides critical insights into the molecular and structural consequences of NKCC1 disruption, contributing to the understanding of its role in KILQS pathogenesis. Further studies are needed to elucidate the precise molecular mechanisms and explore potential therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64188","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T07:16:54Z","timestamp":1752823014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Characterization of a Novel Biallelic\n                    <scp>SLC12A2<\/scp>\n                    Variant Associated With Kilquist Syndrome (\n                    <scp>OMIM<\/scp>\n                    #619080)"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5649-6031","authenticated-orcid":false,"given":"Piero","family":"Leone","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari A. 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Moro  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-0473","authenticated-orcid":false,"given":"Francesca Romana","family":"Lepri","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-8777","authenticated-orcid":false,"given":"Mario","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari A. 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