Key result
Novel homozygous TTN variant links to lethal congenital contracture syndrome, expanding known titinopathies.
Why the study?
Pathogenic variants in the TTN gene cause various cardiomyopathies and skeletal muscle diseases, but their role in lethal congenital contracture syndrome was unclear.
Case Report
Expands the phenotypes caused by pathogenic TTN variants to include lethal congenital contracture syndromes.
TTN variants may cause lethal congenital contracture syndrome; extends titinopathy spectrum but remains hypothesis-generating.
Pathogenic variants in the TTN gene have been reported to cause various cardiomyopathies and a range of skeletal muscle diseases, collectively known as titinopathies. We evaluated a consanguineous family multiple members affected with a lethal congenital contracture syndrome. Using exome sequencing, we identified a homozygous c.36122delC (p. P12041Lfs*20) variant in exon 167 in the fetal IC isoform of TTN. The finding expands the phenotypes that can be caused by pathogenic variants TTN, which should be considered in lethal congenital contracture syndromes, arthrogryposis multiplex congenita, congenital myopathies, and hydrops fetalis.
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Chervinsky et al. (2018) conducted a case report in Lethal congenital contracture syndrome. Homozygous c.36122delC variant in TTN gene was evaluated on Genetic variant identification. A homozygous c.36122delC variant in the TTN gene was identified in a consanguineous family with lethal congenital contracture syndrome, expanding the known phenotypes of titinopathies.
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