{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:00:30Z","timestamp":1783706430297,"version":"3.55.0"},"reference-count":11,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873633"],"award-info":[{"award-number":["81873633"]}],"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":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nemaline myopathy 8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, contractures, fractures, respiratory failure and swallowing difficulties apparent at birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An affected dizygotic twin pair from a non\u2010consanguineous Chinese family presented with severe asphyxia, lethargy and no response to stimuli. The dysmorphic features included prominent nasal bridge, telecanthus, excessive hip abduction, limb edema, absent palmar and sole creases, acromelia, bilateral clubfoot, appendicular hypertonia and cryptorchidism. Both infants died in the first week of life. Whole\u2010exome sequencing was used to identify the causative gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole\u2010exome sequencing identified a recurrent missense variant c.1516A&gt;C and a novel splice\u2010acceptor variant c.1153\u20101G&gt;C in <jats:italic>KLHL40<\/jats:italic> gene in both siblings. We estimated the disease incidence in Southern Chinese population to be 2.47\/100,000 based on the cumulative allele frequency of pathogenic and likely pathogenic variants in our internal database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study expanded the mutation spectrum of <jats:italic>KLHL40<\/jats:italic> and the condition could have been underdiagnosed before. We identified a recurrent missense variant c.1516A&gt;C and provided evidence further supporting the founder effect of this variant in Southern Chinese population. Given the severity of the condition and the relative high incidence, this not\u2010so\u2010rare disorder should be included in expanded carrier screening panel for Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1683","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T09:50:11Z","timestamp":1620813011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel and recurrent <i>KLHL40<\/i> pathogenic variants in a Chinese family of multiple affected neonates with nemaline myopathy 8"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-7701","authenticated-orcid":false,"given":"Sheng","family":"Yi","sequence":"first","affiliation":[{"name":"Genetic and Metabolic Central Laboratory Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children\u2019s Hospital of Guangxi Zhuang Autonomous Region Nanning 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