The structure and function of lamin A/C: Special focus on cardiomyopathy and therapeutic interventions

Tiwari, Vikas; Alam, Md Jahangir; Bhatia, Madhavi; Navya, Malladi; Banerjee, Sanjay K.

doi:10.1016/j.lfs.2024.122489

Cited by 5 publications

(2 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these conditions are Emery–Dreifuss muscular dystrophy, limb-girdle muscular dystrophy 1B, and LMNA -related congenital muscular dystrophy (L-CMD). These laminopathies often exhibit overlapping clinical features, prominently featuring muscle weakness and both cardiac structural alterations and conduction anomalies [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

Martínez Olorón,

Alegría,

Cesar

et al. 2024

IJMS

View full text Add to dashboard Cite

Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.

show abstract

Section: Introductionmentioning

confidence: 99%

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

Martínez Olorón,

Alegría,

Cesar

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Lamins A and C have several pleiotropic effects that may explain why their dysfunction can lead to multiorgan involvement. First, they exert a structural function ensuring nuclear shape, size, and envelope stiffness; moreover, they actively participate in the organization of chromatin and modulation of nucleus–cytoskeleton connections, thereby regulating gene expression [ 2 , 3 ].…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Basic Science Research in Frozen Shoulder: Current Updates

Kim,

Gahlot,

Park

2024

JOIO

View full text Add to dashboard Cite

The structure and function of lamin A/C: Special focus on cardiomyopathy and therapeutic interventions

Cited by 5 publications

References 193 publications

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins

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

Basic Science Research in Frozen Shoulder: Current Updates

Contact Info

Product

Resources

About