Lamin missense mutations—the spectrum of phenotype variability is increasing

Captur, Gabriella; Bilińska, Zofia T.; Arbustini, Eloisa

doi:10.1002/ejhf.1290

Cited by 6 publications

(4 citation statements)

References 15 publications

(31 reference statements)

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“…The results of previous cohorts could have been influenced by the inclusion of nonpathogenic missense variants in previous studies and the different prognoses of some missense variants.10, 14 "Low-risk" LMNA missense variants "Low-risk" missense variants with the founder effect have been described in the literature. As well as the p.Arg331Gln (58 carriers) and p.Arg216Cys (36 carriers) variants, they have been associated with a delayed presentation and a good prognosis vs other pathogenic LMNA variants.15, 16 Captur et al17,18 carried out a study of all LMNA genetic variants published and their relationship with the phenotype described and found that malignant ventricular arrhythmias occur with greater frequency in nonmissense variant carriers. Interestingly, they observed that not all missense variants confer the same prognosis.…”

Section: Differences Between Men and Womenmentioning

confidence: 99%

Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Barriales‐Villa¹,

Ochoa

Larrañaga‐Moreira

et al. 2021

Revista Española de Cardiología (English Edition)

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Section: Differences Between Men and Womenmentioning

confidence: 99%

Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Barriales‐Villa¹,

Ochoa

Larrañaga‐Moreira

et al. 2021

Revista Española de Cardiología (English Edition)

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“…Captur and colleagues analysed published LMNA mutations linked to Lamin heart disease, finding that mutations upstream of the NLS are associated with more severe cardiac phenotypes compared to downstream mutations ( p = 0.014, OR 2.38) [ 40 , 41 ]. Interestingly, they suggested that not all missense variants share the same outcome, and some missense mutations could be as dangerous as non-missense mutations [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience

Forleo,

Carella,

Basile

et al. 2024

Biomedicines

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Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene–phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

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“…Surprisingly, there is little discernible correlation between the location of mutation and the corresponding clinical phenotype for several laminopathy syndromes (with the exception of HGPS). Indeed, cardiac phenotypes have been attributed to mutations spanning exons 1–10 [ 13 , 14 ]. Adding complexity, some pathogenic variants manifest differently in patients; pathogenic LMNA T959 has resulted in DCM, EDMD-like skeletal muscular abnormality, and LGMD-like muscular dystrophy all within the same family [ 15 ].…”

Section: Clinical Consequences: Laminopathy Phenotypes Span Multiple ...mentioning

confidence: 99%

Aberrant chromatin organization at the nexus of laminopathy disease pathways

Santini

Shah

Karnay

et al. 2022

Nucleus

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Lamin missense mutations—the spectrum of phenotype variability is increasing

Cited by 6 publications

References 15 publications

Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience

Aberrant chromatin organization at the nexus of laminopathy disease pathways

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