{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:46:34Z","timestamp":1780523194276,"version":"3.54.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Huzhou science and technology program","award":["2022GY10"],"award-info":[{"award-number":["2022GY10"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p><jats:italic>TTN<\/jats:italic> is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in <jats:italic>TTN<\/jats:italic> have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the <jats:italic>TTN<\/jats:italic> variants.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p><jats:italic>TTN<\/jats:italic> c.38,876\u20132\u00a0A\u2009&gt;\u2009C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant <jats:italic>in trans<\/jats:italic>, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Here we report on three unrelated families presenting with FADS caused by four <jats:italic>TTN<\/jats:italic> variants. In addition, our study demonstrates that pathogenic meta transcript-only <jats:italic>TTN<\/jats:italic> variant can lead to defects which is recognizable prenatally in a recessive manner.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-024-01946-z","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T14:03:01Z","timestamp":1719496981000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of four TTN variants in three families with fetal akinesia deformation sequence"],"prefix":"10.1186","volume":"17","author":[{"given":"Lihong","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqing","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengzhen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyue","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"issue":"8","key":"1946_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.nmd.2021.05.004","volume":"31","author":"H McDermott","year":"2021","unstructured":"McDermott H, Henderson A, Robinson HK, et al. 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