{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:33:08Z","timestamp":1762428788919,"version":"build-2065373602"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Heterozygous missense variants in the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    gene are best known to cause congenital fibrosis of the extraocular muscles. A recent report by Borja et al., 2025 suggested that the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    gene may also be associated with syndromic phenotype, including peripheral neuropathy, brain malformations, and strabismus. We report the second case of early-onset distal motor neuropathy associated with the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    gene. The proband was a 6-year-old female patient who had normal brain MRI, while neurophysiological examination and lower limb muscle MRI both suggested peripheral neuropathy. Quad whole-genome sequencing of the proband, her healthy sibling, and parents identified a\n                    <jats:italic>de novo<\/jats:italic>\n                    missense variant, c.1991T&amp;gt;C, p. (Leu664Pro), in the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    gene and two compound-heterozygous missense variants, c.274C&amp;gt;T, p. (Pro92Ser) and c.512A&amp;gt;G, p. (Asn171Ser), in the\n                    <jats:italic>OXA1L<\/jats:italic>\n                    gene. Since the clinical features were not fully consistent with the known phenotypes associated with\n                    <jats:italic>KIF21A<\/jats:italic>\n                    or\n                    <jats:italic>OXA1L<\/jats:italic>\n                    -related disorders, initial genetic analysis prioritized\n                    <jats:italic>OXA1L<\/jats:italic>\n                    . However, functional studies, including exploratory Western blot analysis and high-resolution respirometry failed to support the pathogenicity of the identified variants. Following the publication of a similar\n                    <jats:italic>KIF21A<\/jats:italic>\n                    -associated case, the c.1991T&amp;gt;C, p. (Leu664Pro) variant was re-evaluated and re-classified as likely pathogenic. Our case supports expansion of the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    -related phenotype to include distal motor neuropathy without brain malformations, in addition to multiple reports of other\n                    <jats:italic>KIF21<\/jats:italic>\n                    -associated syndromic phenotypes. This finding suggests that the\n                    <jats:italic>KIF21A<\/jats:italic>\n                    gene should be considered in the differential diagnosis for patients presenting with childhood-onset distal motor neuropathies.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2025.1699834","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T23:01:57Z","timestamp":1762383717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: autosomal dominant distal motor neuropathy as a new phenotype of KIF21A-related disorders"],"prefix":"10.3389","volume":"16","author":[{"given":"Dmitrii","family":"Subbotin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Tatarskiy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kuchina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Cherevatova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Krylova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana","family":"Ryzhkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41589-024-01638-w","article-title":"The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins","volume":"20","author":"Agarwal","year":"2024","journal-title":"Nat. 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