{
  "abstract": "Background: KBG syndrome (OMIM #148050) is a rare autosomal dominant disorder caused by haploinsufficiency of ANKRD11 on chromosome 16q24.3. Populations outside Western Europe and North America remain underrepresented in the literature, and cohorts that comprehensively evaluate both sequence variants and copy-number variants (CNVs) remain limited.\n\nAims: To characterize the clinical and molecular spectrum of KBG syndrome associated with an identified ANKRD11 alteration in a Turkish multicenter cohort, investigate genotype–phenotype correlations, and assess the contributions of sequence variants and CNVs to disease diagnosis and variant interpretation.\n\nStudy Design: Multicenter, retrospective cohort study.\n\nMethods: We retrospectively evaluated the clinical, anthropometric, and molecular characteristics of 36 Turkish individuals with KBG syndrome and an identified ANKRD11 alteration (31 pathogenic or likely pathogenic variants and five variants of uncertain significance) who were recruited from multiple pediatric genetics centers. Molecular analyses included whole-exome sequencing, clinical exome sequencing, and chromosomal microarray analysis (CMA). Variants were classified according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. An exploratory genotype-phenotype analysis was performed by comparing truncating, non-truncating sequence variant, and CNV/deletion groups using Fisher’s exact and Mann-Whitney U tests, with Benjamini-Hochberg correction for multiple comparisons.\n\nResults: The cohort comprised 22 males and 14 females (male-to-female ratio, 1.57:1). A total of 29 distinct ANKRD11 alterations were identified, including 25 sequence variants and four distinct 16q24.3 deletions. Truncating variants were predominant (n = 25), while 11 sequence variants and four distinct 16q24.3 deletions further expanded the known molecular spectrum of KBG syndrome. The recurrent variant c.1903_1907del (p.Lys635GlnfsTer26) was identified in three unrelated individuals, supporting exon 9 as a major mutational hotspot. All three missense variants were clustered within the C-terminal degron, consistent with the previously reported enrichment of pathogenic missense variants in this functionally important region. 16q24.3 deletions accounted for 19.4% (7/36) of cases, underscoring the diagnostic value of copy-number analysis in patients with suspected KBG syndrome.\n\nConclusion: This study finding expand the clinical and molecular spectrum associated with ANKRD11, provide further evidence supporting haploinsufficiency as the primary disease mechanism, and underscore the diagnostic importance of CMA in syndromic neurodevelopmental disorders. Furthermore, integrating our cohort data with published findings provides a practical framework for interpreting ANKRD11 variants, particularly those involving the 5′ regulatory region and C-terminal missense variants.",
  "abstract_shown": true,
  "affiliations": [
    "Clinic of Medical Genetics, University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, İstanbul, Türkiye",
    "Department of Pediatric Genetics, Ege University Faculty of Medicine, İzmir, Türkiye",
    "Department of Medical Genetics, İstanbul Medeniyet University Faculty of Medicine, İstanbul, Türkiye",
    "Clinic of Medical Genetics, University of Health Sciences Türkiye, Antalya Training and Research Hospital, Antalya, Türkiye",
    "Clinic of Pediatric Genetics, Konya City Hospital, Konya, Türkiye",
    "Department of Medical Genetics, Ordu University Training and Research Hospital, Ordu, Türkiye",
    "Department of Pediatric Genetics, University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, İstanbul, Türkiye",
    "Department of Medical Genetics, Sakarya University Training and Research Hospital, Sakarya, Türkiye",
    "Clinic of Medical Genetics, University of Health Sciences Türkiye, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye",
    "Department of Medical Genetics, Balıkesir University Faculty of Medicine, Balıkesir, Türkiye",
    "Department of Medical Genetics, Marmara University Faculty of Medicine, İstanbul, Türkiye",
    "Clinic of Medical Genetics, University of Health Sciences Türkiye, Zeynep Kamil Women and Children Diseases Training and Research Hospital, İstanbul, Türkiye",
    "Diagnoseq Laboratory, Ankara, Türkiye",
    "Division of Pediatric Genetic Diseases, Clinic of Pediatrics, University of Health Sciences Türkiye, Bursa City Hospital, Bursa, Türkiye",
    "Clinic of Medical Genetics, Dr. Ersin Arslan Training and Research Hospital, Gaziantep, Türkiye",
    "Clinic of Pediatric Genetics, University of Health Sciences Türkiye, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye",
    "Clinic of Genetics, University of Health Sciences Türkiye, Kayseri State Hospital, Kayseri, Türkiye",
    "Department of Medical Genetics, İnönü University Faculty of Medicine, Malatya, Türkiye"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 29,
  "authors": [
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        0
      ],
      "name": "İrem Kalay",
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    },
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        1
      ],
      "name": "Tahir Atik",
      "orcid": "0000-0002-1142-3872"
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        2
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      "name": "Elif Yılmaz Güleç",
      "orcid": "0000-0003-0872-3898"
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      "name": "Aysel Ünal",
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        3
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      "name": "Mine Balasar",
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        4
      ],
      "name": "Hayriye Nermin Keçeci",
      "orcid": "0000-0002-1136-6038"
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        5
      ],
      "name": "Çağrı Doğan",
      "orcid": "0000-0001-5068-0380"
    },
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        6
      ],
      "name": "Esra Usluer",
      "orcid": "0000-0003-4849-2078"
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    {
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        6
      ],
      "name": "Burcu Yeter",
      "orcid": "0000-0002-6255-1057"
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    {
      "affs": [
        7
      ],
      "name": "Kübra Ateş",
      "orcid": "0000-0002-0669-8230"
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    {
      "affs": [
        8
      ],
      "name": "Alper Gezdirici",
      "orcid": "0000-0002-2432-9279"
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    {
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        9
      ],
      "name": "Hilmi Bolat",
      "orcid": "0000-0001-6574-8149"
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    {
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        1
      ],
      "name": "Kübra Taşar",
      "orcid": "0000-0002-8965-2907"
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    {
      "affs": [
        9
      ],
      "name": "Zeynep Esener",
      "orcid": "0000-0001-6579-6132"
    },
    {
      "affs": [
        10
      ],
      "name": "Esra Dirimtekin",
      "orcid": "0009-0008-5811-4234"
    },
    {
      "affs": [
        11
      ],
      "name": "Sümeyra Oğuz",
      "orcid": "0000-0003-4001-0505"
    },
    {
      "affs": [
        12
      ],
      "name": "Oğuzhan Bahadır",
      "orcid": "0000-0003-2201-0974"
    },
    {
      "affs": [
        2
      ],
      "name": "Süheyla Emre",
      "orcid": "0009-0008-8403-7834"
    },
    {
      "affs": [
        13
      ],
      "name": "Öznur Yılmaz Bayer",
      "orcid": "0000-0002-1883-0278"
    },
    {
      "affs": [
        14
      ],
      "name": "Abdullah İhsan Gürler",
      "orcid": "0000-0002-9034-715X"
    },
    {
      "affs": [
        14
      ],
      "name": "Uğur Gümüş",
      "orcid": "0000-0003-0024-9079"
    },
    {
      "affs": [
        1
      ],
      "name": "Yusuf Can Doğan",
      "orcid": "0009-0004-6917-8090"
    },
    {
      "affs": [
        15
      ],
      "name": "Serdar Bozlak",
      "orcid": "0000-0001-7275-431X"
    },
    {
      "affs": [
        8
      ],
      "name": "Halil İbrahim Yılmaz",
      "orcid": "0009-0000-0342-9900"
    },
    {
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        16
      ],
      "name": "Sema Nur Kır",
      "orcid": "0009-0006-6680-8856"
    },
    {
      "affs": [
        16
      ],
      "name": "Hilal Akalın",
      "orcid": "0000-0002-2580-836X"
    },
    {
      "affs": [
        16
      ],
      "name": "Aslıhan Kiraz",
      "orcid": "0000-0001-7317-2717"
    },
    {
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        17
      ],
      "name": "İbrahim Tekedereli",
      "orcid": "0000-0002-3300-8020"
    },
    {
      "affs": [
        16
      ],
      "name": "Munis Dündar",
      "orcid": "0000-0003-0969-4611"
    }
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  "bibtex": "https://research.draconitic.com/paper/56yzg19nbrgyf.bib",
  "cited_by": 0,
  "doi": "10.4274/balkanmedj.galenos.2026.2026-7-44",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725044/",
  "id": "56yzg19nbrgyf",
  "issns": [
    "2146-3123",
    "2146-3131"
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  "landing_url": "https://doi.org/10.4274/balkanmedj.galenos.2026.2026-7-44",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "heading",
      "Original Article"
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  "pdf_url": null,
  "pmcid": "PMC13725044",
  "pmid": "42808190",
  "published": "2026-11-02",
  "publisher": "Trakya University Faculty of Medicine",
  "ris": "https://research.draconitic.com/paper/56yzg19nbrgyf.ris",
  "sources": [
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      "subfield": "genetics-genomics"
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  "title": "Clinical and Molecular Spectrum of KBG Syndrome in the Largest Independent Turkish Cohort",
  "title_text": "Clinical and Molecular Spectrum of KBG Syndrome in the Largest Independent Turkish Cohort",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:24Z",
  "url": "https://research.draconitic.com/paper/56yzg19nbrgyf",
  "venue": "Balkan Medical Journal",
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