Genotype-phenotype correlations in recessive titinopathies.

Details

Serval ID
serval:BIB_481E89CF0E7E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genotype-phenotype correlations in recessive titinopathies.
Journal
Genetics in medicine
Author(s)
Savarese M., Vihola A., Oates E.C., Barresi R., Fiorillo C., Tasca G., Jokela M., Sarkozy A., Luo S., Díaz-Manera J., Ehrstedt C., Rojas-García R., Sáenz A., Muelas N., Lonardo F., Fodstad H., Qureshi T., Johari M., Välipakka S., Luque H., Petiot P., de Munain A.L., Pane M., Mercuri E., Torella A., Nigro V., Astrea G., Santorelli F.M., Bruno C., Kuntzer T., Illa I., Vílchez J.J., Julien C., Ferreiro A., Malandrini A., Zhao C.B., Casar-Borota O., Davis M., Muntoni F., Hackman P., Udd B.
ISSN
1530-0366 (Electronic)
ISSN-L
1098-3600
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
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).
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).
Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.
Keywords
arthrogryposis, cardiomyopathy, congenital myopathy, skeletal muscle disorders, titin
Pubmed
Create date
17/08/2020 10:24
Last modification date
21/08/2020 6:26
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