{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:52:15Z","timestamp":1790117535119,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Nemaline myopathy (NEM) is a rare congenital muscular disorder characterized by slow progression or static neuromuscular symptoms, which is mainly caused by variants in genes encoding the myofilament protein of skeletal muscle sarcomere. This study aimed to conduct prenatal diagnosis and functional analysis of variants in the\n KLHL40<\/jats:italic>\n gene causing NEM 8.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A Chinese family who experienced multiple pregnancies with recurrent prenatal ultrasound anomalies (such as clubfoot and polyhydramnios) and subsequent neonatal death was enrolled in this study. Etiology diagnosis was conducted using karyotype, chromosomal microarray analysis (CMA), and exome sequencing (ES). Quantitative real\u2010time reverse transcription polymerase chain reaction (qPCR) and western blotting were performed to investigate the transcription and expression levels of the defective gene. Hematoxylin\u2013eosin (HE) stain and modified Gomori staining were used for further pathological examination.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n No chromosomal abnormalities were detected by karyotype and CMA in the proband of this family. However, the ES results revealed two compound heterozygous variants in\n KLHL40<\/jats:italic>\n gene NM_152393.4:c.[1516A>\u2009C p.(T506P)]; [1327G>\u2009A p.(G443S)] in the fetus. The c.1516A>\u2009C p.(T506P) variant was interpreted as pathogenic, whereas the p.G443S variant was rarely reported and classified as a variant of uncertain significance. Interestingly, the subsequent western blotting analysis elicited a significantly decreased expression level of KLHL40 protein in fetal skeletal muscle tissues compared with the controls. In addition, the HE and modified Gomori stains demonstrated nemaline bodies in the fetus using skeletal muscle tissue.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Combining prenatal ultrasound and ES testing increases diagnostic yield among NEM\u2010affected fetuses. Our results extend the mutational spectrum of the pathogenic\n KLHL40<\/jats:italic>\n variant c.1327G>\u2009A p.(G443S) linked to NEM8 and aid genotype\u2013phenotype correlation analysis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70270","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:48:47Z","timestamp":1783666127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Diagnosis and Functional Analysis of Two Compound Heterozygous Variants in the\n \n KLHL40<\/i>\n <\/scp>\n Gene Causing Nemaline Myopathy 8"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-205X","authenticated-orcid":false,"given":"Jianlong","family":"Zhuang","sequence":"first","affiliation":[{"name":"Prenatal Diagnosis Center Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pathology Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiumei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac272"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74994"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2017.10.003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlz056"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.937668"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31940-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.9.705"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32042-7"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5172"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.004"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-019-09519-9"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/86.4.793"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.04.031"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgc4.1045"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1229"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1683"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02306-9"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.816090"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-021-03589-9"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13039-019-0461-1"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70270","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T14:50:17Z","timestamp":1785077417000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mgg3.70270"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70270","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70270"}}