{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:47:35Z","timestamp":1775612855951,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071462"],"award-info":[{"award-number":["82071462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>CHKB<\/jats:italic>mutations have been described in 49 patients with megaconial congenital muscular dystrophy, which is a rare autosomal recessive disorder, of which 40 patients showed homozygosity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood genomic DNA samples were extracted from patients and their parents and were tested by whole exome sequencing. Quantitative PCR was performed to detect deletion. Single nucleotide polymorphism analysis was performed to identify uniparental disomy. Quantitative PCR and western blot were used to measure the expression level of<jats:italic>CHKB<\/jats:italic>in patient 1\u2010derived immortalized lymphocytes. Mitochondria were observed in lymphocytes by electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two unrelated cases born to non\u2010consanguineous parents were diagnosed with megaconial congenital muscular dystrophy due to apparently homozygous mutations (patient 1: c.225\u20102A&gt;T; patient 2: c.701C&gt;T) in the<jats:italic>CHKB<\/jats:italic>gene using whole exome sequencing. Quantitative PCR revealed that patient 1 had a large deletion encompassing the<jats:italic>CHKB<\/jats:italic>gene, inherited from the mother. Single nucleotide polymorphism analysis revealed patient 2 had paternal uniparental isodisomy containing the<jats:italic>CHKB<\/jats:italic>gene. In the immortalized lymphocytes from patient 1, decreased expression of<jats:italic>CHKB<\/jats:italic>was revealed by quantitative PCR and western blot, and giant mitochondria were observed using electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide a possibility to detect giant mitochondria in other cells when muscle was not available. Moreover, clinicians should be aware that homozygous variants can be masqueraded by uniparental disomy or large deletions in offspring of non\u2010consanguineous parents, and excessive homozygosity may be misdiagnosed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2162","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T09:26:03Z","timestamp":1678440363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Large heterozygous deletion and uniparental disomy masquerading as homozygosity in<i>CHKB<\/i>gene"],"prefix":"10.1002","volume":"11","author":[{"given":"Tenghui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciliu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-2140","authenticated-orcid":false,"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-6962","authenticated-orcid":false,"given":"Jing","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Xiangya Hospital of Central South University Changsha China"},{"name":"Clinical Research Center for Children Neurodevelopmental disabilities of Hunan Province Xiangya Hospital of Central South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00913-1"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.11.002"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70271-6"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2015.05.008"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2014.06.005"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.10.009"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.83"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25183"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2015.09.018"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22387"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9856-2"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2760(97)00118-5"},{"issue":"23","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"694","DOI":"10.4103\/aian.AIAN_98_19","article-title":"A rare cause of autism Spectrum disorder: Megaconial muscular dystrophy","volume":"5","author":"Kutluk G.","year":"2020","journal-title":"Annals of Indian Academy of Neurology"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2019.04.002"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328364c82d"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.010"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.04.002"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"issue":"69","key":"e_1_2_12_20_1","first-page":"657","article-title":"Congenital megaconial myopathy due to a novel defect in the choline kinase beta gene","volume":"5","author":"R\u00edos P. G.","year":"2012","journal-title":"Archives of Neurology"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<452::AID-BIES7>3.0.CO;2-K"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000520502"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2016.02.001"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-022-01056-7"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2162","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2162","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T17:48:48Z","timestamp":1702057728000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/mgg3.2162"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2162","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]},"assertion":[{"value":"2022-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2162"}}