Toggle Main Menu Toggle Search

Open Access padlockePrints

Genotype–phenotype correlations in recessive titinopathies

Lookup NU author(s): Dr Rita Barresi, Professor Giorgio TascaORCiD, Professor Jordi Diaz ManeraORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


© 2020, American College of Medical Genetics and Genomics. Purpose: High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype–phenotype correlations in this cohort. Methods: We analyzed clinical and genetic data in a cohort of patients with biallelic pathogenic or likely pathogenic TTN variants. The cohort included both previously reported cases (100 patients from 81 unrelated families) and unreported cases (23 patients from 20 unrelated families). Results: Overall, 132 causative variants were identified in cohort members. More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene. The remaining patients had a distal or proximal phenotype and a childhood or later (noncongenital) onset. All noncongenital cases had at least one pathogenic variant in one of the final three TTN exons (362–364). Conclusion: Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.

Publication metadata

Author(s): Savarese M, Vihola A, Oates EC, Barresi R, Fiorillo C, Tasca G, Jokela M, Sarkozy A, Luo S, Diaz-Manera J, Ehrstedt C, Rojas-Garcia R, Saenz A, Muelas N, Lonardo F, Fodstad H, Qureshi T, Johari M, Valipakka S, Luque H, Petiot P, de Munain AL, Pane M, Mercuri E, Torella A, Nigro V, Astrea G, Santorelli FM, Bruno C, Kuntzer T, Illa I, Vilchez JJ, Julien C, Ferreiro A, Malandrini A, Zhao C-B, Casar-Borota O, Davis M, Muntoni F, Hackman P, Udd B

Publication type: Article

Publication status: Published

Journal: Genetics in Medicine

Year: 2020

Volume: 22

Pages: 2029-2040

Print publication date: 01/12/2020

Online publication date: 11/08/2020

Acceptance date: 16/07/2020

ISSN (print): 1098-3600

ISSN (electronic): 1530-0366

Publisher: Springer Nature


DOI: 10.1038/s41436-020-0914-2


Altmetrics provided by Altmetric