Author:
Qi Yiming,Ji Xueqi,Ding Hongke,Wang Yunan,Liu Xin,Zhang Yan,Yin Aihua
Abstract
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 3–6 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>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.
Funder
Guangdong Medical Research Foundation
Science and Technology Planning Project of Guangdong Province
Basic and Applied Basic Research Foundation of Guangdong Province
Subject
Genetics (clinical),Genetics,Molecular Medicine
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献