{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:42:15Z","timestamp":1778751735670,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in <jats:italic>C12orf4<\/jats:italic>. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patients carry a novel homozygous nonsense <jats:italic>C12orf4<\/jats:italic> variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of <jats:italic>C12orf4<\/jats:italic> defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This rather nonsyndromic and nonspecific clinical picture implies that additional patients with <jats:italic>C12orf4<\/jats:italic> defects will likely continue to be identified using the \u201cgenotype\u2010first\u201d approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.865","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T09:40:15Z","timestamp":1563874815000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel variant of <i>C12orf4<\/i> in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-8862","authenticated-orcid":false,"given":"Miroslava","family":"Hancarova","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech 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