{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:46:27Z","timestamp":1780523187785,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["B2022082"],"award-info":[{"award-number":["B2022082"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1414020008"],"award-info":[{"award-number":["2021A1414020008"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515111000"],"award-info":[{"award-number":["2019A1515111000"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Variants in TTN are associated with a broad range of clinical phenotypes, from dominant adult-onset dilated cardiomyopathy to recessive infantile-onset myopathy. However, few foetal cases have been reported for multiple reasons. Next-generation sequencing has facilitated the prenatal identification of a growing number of suspected titinopathy variants. We investigated six affected foetuses from three families, completed the intrauterine course of the serial phenotypic spectrum of TTN, and discussed the genotype-phenotype correlations from a broader perspective. The recognizable prenatal feature onset at the second trimester was started with reduced movement, then contracture 3\u20136 weeks later, followed with\/without hydrops, finally at late pregnancy was accompanied with polyhydramnio (major) or oligohydramnios. Two cases with typical arthrogryposis-hydrops sequences identified a meta-only transcript variant c.36203-1G&amp;gt;T. Deleterious transcriptional consequences of the substitution were verified by minigene splicing analysis. Case 3 identified a homozygous splicing variant in the constitutively expressed Z-disc. It presented a milder phenotype than expected, which was presumably saved by the isoform of corons. A summary of the foetal-onset titinopathy cases implied that variants in TTN present with a series of signs and a spectrum of clinical severity, which followed the dosage\/positional effect; the meta-only transcript allele involvement may be a prerequisite for the development of fatal hydrops.<\/jats:p>","DOI":"10.3389\/fgene.2022.1064474","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T17:17:02Z","timestamp":1674667022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A spectrum of clinical severity of recessive titinopathies in prenatal"],"prefix":"10.3389","volume":"13","author":[{"given":"Yiming","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqi","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongke","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1161\/hh2301.100981","article-title":"The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system","volume":"89","author":"Bang","year":"2001","journal-title":"Circulation Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/humu.23938","article-title":"Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy","volume":"41","author":"Bryen","year":"2020","journal-title":"Hum. 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