{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:13:22Z","timestamp":1783649602649,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"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":["81800110"],"award-info":[{"award-number":["81800110"]}],"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;amp; Gen Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Charcot\u2013Marie\u2013Tooth (CMT) disease is the most frequent hereditary motor sensory neurological disease. GJB1 gene is the second most frequent cause of CMT, accounting for approximately 10% of CMT cases worldwide. We identified a large Han family with X\u2010linked CMT disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the probands and his mother underwent electrophysiological examinations and other family members were assessed retrospectively. Whole\u2010exome sequencing, Sanger sequencing, and SNP array linkage analysis were performed to find and confirm the variant. The functional effect of the identified variant was further investigated in HEK293 cells and MCF\u20107 cells by minigene splicing assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The affected individuals had some clinical symptoms including symmetric atrophy and progressive weakness of the distal muscles in their twenties. Electrophysiological examinations result in peripheral nerve injury of the upper and lower limbs. Whole\u2010exome sequencing identified a novel hemizygous deletion mutation (NM_000166: c.\u201016\u20108_\u201014del) in the GJB1 gene. SNP array linkage analysis and co\u2010segregation analysis confirmed this mutation. Minigene splicing assay verified that this mutation leads to the activation of cryptic splicing sites in exon 2 which results in the deletion of exon 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study provides theoretical guidance for prenatal diagnosis and subsequent fertility of this family. This result expands the spectrum of mutations in GJB1 known to be associated with CMTX and contributes to the diagnosis of CMT and clinical genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2108","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T11:09:36Z","timestamp":1668683376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel splicing mutation in 5'<scp>UTR<\/scp> of <scp>GJB1<\/scp> causes X\u2010linked Charcot\u2014Marie\u2013tooth disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-198X","authenticated-orcid":false,"given":"MeiYi","family":"Li","sequence":"first","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Yin","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8730-8520","authenticated-orcid":false,"given":"Peng","family":"Du","sequence":"additional","affiliation":[{"name":"Genetic Testing Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443706"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.303"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11010024"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0238-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12327"},{"key":"e_1_2_9_7_1","first-page":"235","article-title":"The genetics of Charcot\u2010Marie\u2010tooth disease: Current trends and future implications for diagnosis and management","volume":"8","author":"Hoyle J. 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