{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:31:48Z","timestamp":1791232308505,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole\u2010exome sequencing (WES)\u2010based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700\u00a0genes have been reported in syndromic and non\u2010syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and <jats:italic>in silico<\/jats:italic> analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate\u2010to\u2010severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Filtering the data identified by WES, two novel homozygous missense variants in <jats:italic>FBXO31<\/jats:italic> and <jats:italic>TIMM50<\/jats:italic>\u00a0genes and one previously reported mutation in the <jats:italic>CEP290<\/jats:italic>\u00a0gene in the probands were found. Sanger sequencing confirmed the homozygote variant's presence of <jats:italic>TIMM50<\/jats:italic> and <jats:italic>FBXO31<\/jats:italic>\u00a0genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24241","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T12:10:00Z","timestamp":1641989400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families"],"prefix":"10.1002","volume":"36","author":[{"given":"Mahdiyeh","family":"Moudi","sequence":"first","affiliation":[{"name":"Department of Genetics Shahid Sadoughi University of Medical Sciences Yazd Iran"},{"name":"Genetics of Non\u2010Communicable Disease Research Center Zahedan University of Medical Sciences Zahedan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Yahya","family":"Vahidi Mehrjardi","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Center Shahid Sadoughi University of Medical Sciences Yazd Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Hozhabri","sequence":"additional","affiliation":[{"name":"Medical Bioinformatician Centogene Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Metanat","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Medicine Zahedan University of Medical Sciences Zahedan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mehdi","family":"Kalantar","sequence":"additional","affiliation":[{"name":"Department of Genetics Shahid Sadoughi University of Medical Sciences Yazd Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Taheri","sequence":"additional","affiliation":[{"name":"Genetics of Non\u2010Communicable Disease Research Center Zahedan University of Medical Sciences Zahedan Iran"},{"name":"Department of Genetics School of Medicine Zahedan University of Medical Sciences Zahedan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Abortion Research Centre Yazd Reproductive Sciences Institute Shahid Sadoughi University of Medical Sciences Yazd Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-9438","authenticated-orcid":false,"given":"Mohammadreza","family":"Dehghani","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Center Shahid Sadoughi University of Medical Sciences Yazd Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5223\/pghn.2021.24.1.1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1843-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23484"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11040361"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13882"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-021-00188-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000360539"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1751-0473-9-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2018.03.024"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1190-7"},{"key":"e_1_2_10_12_1","unstructured":"WeeksNT LueckeGR editors.Performance analysis and optimization of SAMtools sorting. 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