{ "abstract": "Background In males, MECP2 loss of function was long thought to be lethal or uniformly severe, and affected boys remain under-recognised. Their clinical range is still poorly defined. Methods We assembled a multicentre Turkish series of 22 hemizygous male probands ascertained through routine diagnostic testing rather than severe-phenotype registries. Variants were classified under the ClinGen Expert Panel specification for MECP2 (GN036, version 6.0.0) and its combining rules, with the Panel’s ClinVar classifications adopted where available. Phenotypic analysis was restricted to the 21 probands with pathogenic, likely pathogenic or uncertain variants. Results The 22 probands carried 17 distinct variants (11 missense, 5 frameshift and one 3’ untranslated region deletion), of which 2 were classified as pathogenic, 1 likely pathogenic, 13 uncertain and 1 benign (3, 4, 14 and 1 probands, respectively). Where recorded, intellectual disability or developmental delay affected 7 of 7 probands with pathogenic or likely pathogenic variants and 8 of 10 with uncertain variants; seizures affected 2 of 3 and 8 of 10, respectively. Growth or head-circumference findings, recorded in 9 of 21 probands, included obesity or overgrowth (5), microcephaly (4, one borderline) and short stature (3). A maternal carrier was identified in 6 of 22 families (five laboratory-confirmed); the other 16 mothers were untested, so no de novo event was confirmed. Second-locus findings, reported by referring laboratories in 3 probands, could not be independently reclassified. Conclusions In this diagnostically ascertained series, phenotypes observed among males carrying MECP2 variants were graded rather than uniformly severe. Fourteen of the 21 probands carry variants of uncertain significance, in whom causation is not established, so the range that may be attributed to MECP2 rests on seven individuals carrying variants classified as pathogenic or likely pathogenic under the stated criteria. In one of them, published functional data on the identical variant conflict with its pathogenic classification, so attribution of his phenotype to MECP2 remains uncertain. These provisional observations support a low threshold for MECP2 testing in males with unexplained neurodevelopmental presentations, attention to growth as well as head circumference, and consideration of additional loci.", "abstract_shown": true, "affiliations": [ "Department of Medical Genetics, Ordu University Training and Research Hospital", "Detagen Genetic Diagnosis Center", "Department of Pediatric Neurology, Faculty of Medicine, Karadeniz Technical University", "Department of Medical Genetics, Batman Training and Research Hospital", "Department of Medical Genetics, Dr. Ersin Arslan Training and Research Hospital", "Department of Medical Genetics, Ankara Etlik City Hospital", "Department of Medical Genetics, Cerrahpaşa University Hospital", "Department of Medical Genetics, Medeniyet University Hospital", "Department of Medical Genetics, Gazi Yaşargil Training and Research Hospital", "Department of Medical Genetics, Adnan Menderes University Hospital", "Department of Medical Genetics, Balıkesir University Hospital", "Department of Child and Adolescent Psychiatry, Balıkesir University Hospital", "Gelişim Medical Diagnostic Center", "Genetic Diseases Diagnosis and Evaluation Center, İstinye University", "Department of Pediatric Genetics, Ankara Etlik City Hospital", "Department of Medical Genetics, Ankara Bilkent City Hospital", "Department of Medical Genetics, Gazi University", "Department of Medical Genetics, Trabzon Kanuni Training and Research Hospital", "Department of Medical Genetics, Zeynep Kamil Women’s and Children’s Diseases Training and Research Hospital", "Hamidiye International School of Medicine, Kartal Dr. Lütfi Kırdar City Hospital, University of Health Sciences Türkiye", "Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University", "Ankara Bilkent City Hospital, Health Institutes of Türkiye (TÜSEB)", "Department of Medical Genetics, University of Health Sciences Sisli Hamidiye Etfal Training and Research Hospital" ], "article_type": null, "arxiv": null, "author_total": 34, "authors": [ { "affs": [ 0 ], "name": "Çağrı Doğan" }, { "affs": [ 1 ], "name": "Mehmet Burak Mutlu" }, { "affs": [ 2 ], "name": "Ali Cansu" }, { "affs": [ 3 ], "name": "Esra Habiloğlu" }, { "affs": [ 3 ], "name": "Murat Öztürk" }, { "affs": [ 4 ], "name": "Uğur Gümüş" }, { "affs": [ 4 ], "name": "Abdullah İhsan Gürler" }, { "affs": [ 4 ], "name": "Bahtiyar Şahinoğlu" }, { "affs": [ 4 ], "name": "Hamdi Kale" }, { "affs": [ 5 ], "name": "Mustafa Tarık Alay" }, { "affs": [ 5 ], "name": "Abdullah Sezer" }, { "affs": [ 6 ], "name": "Aysel Kalaycı" }, { "affs": [ 7 ], "name": "Elif Yılmaz Güleç" }, { "affs": [ 7 ], "name": "Süheyla Emre" }, { "affs": [ 8 ], "name": "Hamza Polat" }, { "affs": [ 9 ], "name": "Zehra Manav Yiğit" }, { "affs": [ 10 ], "name": "Hilmi Bolat" }, { "affs": [ 10 ], "name": "Zeynep Esener" }, { "affs": [ 10 ], "name": "Dilan Genç Akdağ" }, { "affs": [ 11 ], "name": "Gül Ünsel Bolat" }, { "affs": [ 12 ], "name": "Ayberk Türkyılmaz" }, { "affs": [ 13 ], "name": "Akif Ayaz" }, { "affs": [ 14 ], "name": "Abdulkerim Kolkıran" }, { "affs": [ 15 ], "name": "Ahmet Cevdet Ceylan" }, { "affs": [ 15 ], "name": "Taha Solmaz" }, { "affs": [ 16 ], "name": "Yusuf Bahap" }, { "affs": [ 17 ], "name": "Neslihan Cinkara" }, { "affs": [ 18 ], "name": "Sümeyra Oğuz" }, { "affs": [ 18 ], "name": "Elif Uzay" }, { "affs": [ 19 ], "name": "Safiye Güneş Sager" }, { "affs": [ 20 ], "name": "Alper Han Çebi" }, { "affs": [ 20 ], "name": "Oğuzhan Demir" }, { "affs": [ 21 ], "name": "Ezgi Susam" }, { "affs": [ 22 ], "name": "İrem Kalay" } ], "bibtex": "https://research.draconitic.com/paper/aq1hkfpqx0wnw.bib", "cited_by": 0, "doi": "10.1186/s12887-026-07905-0", "fulltext_url": "https://doi.org/10.1186/s12887-026-07905-0", "id": "aq1hkfpqx0wnw", "issns": [ "1471-2431" ], "landing_url": "https://doi.org/10.1186/s12887-026-07905-0", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RJ1-570" ], [ "openalex", "1311|Genetics and Neurodevelopmental Disorders" ] ], "openalex": "W7223155137", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-25", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/aq1hkfpqx0wnw.ris", "sources": [ { "first_seen": "2026-10-30T13:46:26Z", "native_id": "d0eb73a0f2084afa9a86b77f888f0bd8", "source": "doaj", "url": "https://doi.org/10.1186/s12887-026-07905-0" } ], "subjects": [ { "field": "biology", "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders", "subfield": "genetics-genomics" } ], "title": "The clinical spectrum of MECP2 variants in males: a multicenter Turkish cohort of 22 probands, with implications for diagnosis and variant interpretation", "title_text": "The clinical spectrum of MECP2 variants in males: a multicenter Turkish cohort of 22 probands, with implications for diagnosis and variant interpretation", "type": "peer-reviewed", "updated_at": "2026-10-30T13:46:26Z", "url": "https://research.draconitic.com/paper/aq1hkfpqx0wnw", "venue": "BMC Pediatrics", "versions": [] }