{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T22:33:15Z","timestamp":1777329195102,"version":"3.51.4"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Monoallelic\n                    <jats:italic>KIF11<\/jats:italic>\n                    variants are associated with\n                    <jats:italic>Microcephaly with or without Chorioretinopathy, Lymph-edema, or Impaired Intellectual Development (MCLMR) (OMIM:152950)<\/jats:italic>\n                    . This study presents seven patients from two distinct families, exhibiting extreme clinical heterogeneity, along with novel clinical findings and genetic variants. Patient 1 presented with learning difficulties, epilepsy, behavioral abnormalities, and various ocular anomalies, in addition to microcephaly and facial dysmorphism. Patient 2 was prenatally diagnosed with dorsal pedal edema, which was confirmed postnatally, alongside facial dysmorphic features and the need for craniosynostosis surgery at four months. Peripheral blood samples were obtained for DNA isolation, and\n                    <jats:italic>Whole Exome Sequencing (WES)<\/jats:italic>\n                    was performed for molecular analysis. Whole-exome sequencing (WES) revealed a de novo heterozygous frameshift variant in the\n                    <jats:italic>KIF11<\/jats:italic>\n                    gene (NM_004523.4: c.2224_2225del; p. Asn742TyrfsTer6) in patient 1, and a novel heterozygous frameshift variant (NM_004523.4: c.2946dup; p. Leu983SerfsTer6) in the same gene in patient 2. Segregation analysis demonstrated that Patient 2's variant was inherited from the mother and was also present in the maternal grandmother, sister, and two aunts. Our findings highlight the broad clinical heterogeneity of MCLMR syndrome, as Patient 1 exhibited keratoconus, optic nerve hypoplasia, behavioral problems, and seizures, which are rarely reported. Additionally, Patient 2 represents the first documented patient of prenatal lymphedema detection in MCLMR syndrome. Furthermore, craniosynostosis, identified in two patients (P2 and P5), has not been previously described, suggesting a potential novel phenotypic feature. These findings expand the genotypic and phenotypic spectrum of\n                    <jats:italic>KIF11<\/jats:italic>\n                    -related disease.\n                  <\/jats:p>","DOI":"10.2478\/bjmg-2025-0001","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:56:51Z","timestamp":1759985811000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <i>KIF11<\/i>\n                    Variants with New Clinical Features: Expanding the Clinical Phenotype"],"prefix":"10.2478","volume":"28","author":[{"given":"T","family":"Apuhan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Saglam Kubra","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Bebek","sequence":"additional","affiliation":[{"name":"Karadeniz Technical University, Faculty of Medicine , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.A","family":"Demiroglu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.A","family":"Cebi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Turkyilmaz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2026042716343901793_j_bjmg-2025-0001_ref_001","doi-asserted-by":"crossref","unstructured":"Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, et al. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet. 2012 Feb 10;90(2):356\u201362.","DOI":"10.1016\/j.ajhg.2011.12.018"},{"key":"2026042716343901793_j_bjmg-2025-0001_ref_002","doi-asserted-by":"crossref","unstructured":"Jones GE, Ostergaard P, Moore AT, Connell FC, Williams D, Quarrell O, et al. Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations. Eur J Hum Genet. 2014 Jul;22(7):881\u20137.","DOI":"10.1038\/ejhg.2013.263"},{"key":"2026042716343901793_j_bjmg-2025-0001_ref_003","doi-asserted-by":"crossref","unstructured":"Mirzaa GM, Collins S, Dobyns WB. Corrigendum to \u201cCongenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: Five novel mutations and review of the literature. Am J Med Genet Part A 2014 164A:2879-86\u201d. Am J Med Genet A. 2016 Feb;170(2):547.","DOI":"10.1002\/ajmg.a.37449"},{"key":"2026042716343901793_j_bjmg-2025-0001_ref_004","doi-asserted-by":"crossref","unstructured":"Mears K, Bakall B, Harney LA, Penticoff JA, Stone EM. Autosomal Dominant Microcephaly Associated With Congenital Lymphedema and Chorioretinopathy Due to a Novel Mutation in KIF11. JAMA Ophthalmol. 2015 Jun;133(6):720\u20131.","DOI":"10.1001\/jamaophthalmol.2015.199"},{"key":"2026042716343901793_j_bjmg-2025-0001_ref_005","doi-asserted-by":"crossref","unstructured":"Schl\u00f6gel MJ, Mendola A, Fastr\u00e9 E, Vasudevan P, Devriendt K, de Ravel TJ, et al. No evidence of locus heterogeneity in familial microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome. Orphanet J Rare Dis. 2015 May 2;10:52.","DOI":"10.1186\/s13023-015-0271-4"},{"key":"2026042716343901793_j_bjmg-2025-0001_ref_006","doi-asserted-by":"crossref","unstructured":"Leung AK. 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