ArticleBMC medical genetics2014
Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2).
Article in BMC medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Geno- and phenotypic characteristics and clinical outcomes ofFrontiers in cardiovascular medicine · 2022Pooled it
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- Inactivation influences the extent of inhibition of voltage-gated CaFrontiers in physiology · 2023Article
- Impaired CaJournal of molecular and cellular cardiology · 2022Article
- CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms.The Journal of general physiology · 2022Article
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Update on the Molecular Genetics of Timothy Syndrome.Frontiers in pediatrics · 2021Review
- Voltage-Gated CaFrontiers in synaptic neuroscience · 2021Review
- Cav1.2 channelopathies causing autism: new hallmarks on Timothy syndrome.Pflugers Archiv : European journal of physiology · 2020Review
- Practical Aspects in Genetic Testing for Cardiomyopathies and Channelopathies.The Clinical biochemist. Reviews · 2019Review
- A missense mutation in SNRPE linked to non-syndromal microcephaly interferes with U snRNP assembly and pre-mRNA splicing.PLoS genetics · 2019Article
- Dysfunctional Cav1.2 channel in Timothy syndrome, from cell to bedside.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Impaired chromaffin cell excitability and exocytosis in autistic Timothy syndrome TS2-neo mouse rescued by L-type calcium channel blockers.The Journal of physiology · 2019Article
- Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.Molecular genetics & genomic medicine · 2019Article
- Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia.Channels (Austin, Tex.) · 2018Review
- Genetic Testing in Inherited Heart Diseases: Practical Considerations for Clinicians.Current cardiology reports · 2017Review
- Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis in Long QT Syndrome Type 8:Frontiers in physiology · 2017Article
- Pro-arrhythmogenic effects of CACNA1C G1911R mutation in human ventricular tachycardia: insights from cardiac multi-scale models.Scientific reports · 2016Article
- Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.Science (New York, N.Y.) · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong-QT syndrome (LQTS) causes a prolongation of the QT-interval in the ECG leading to life threatening tachyarrhythmia and ventricular fibrillation. One atypical form of LQTS, Timothy syndrome (TS), is associated with syndactyly, immune deficiency, cognitive and neurological abnormalities as well as distinct cranio-facial abnormalities. CASE PRESENTATION: On a family with both children diagnosed with clinical LQTS, we performed whole exome sequencing to comprehensively screen for causative mutations after a targeted candidate gene panel screen for Long-QT syndrome target genes failed to identify any underlying genetic defect. Using exome sequencing, we identified in both affected children, a p.402G > S mutation in exon 8 of the CACNA1C gene, a voltage-dependent Ca2+ channel. The mutation was inherited from their father, a mosaic mutation carrier. Based on this molecular finding and further more careful clinical examination, we refined the diagnosis to be Timothy syndrome (TS2) and thereby were able to present new therapeutic approaches.
conclusionsOur study highlights the difficulties in accurate diagnosis of patients with rare diseases, especially those with atypical clinical manifestation. Such challenge could be addressed with the help of comprehensive and unbiased mutation screening, such as exome sequencing.
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