Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations

Lamin A/C mutations in dilated cardiomyopathy

“…The rod domain comprises several coiled-coil domains separated by linker regions which are evolutionarily highly conserved ( Fig. 1) [16].…”

“…However, hot spot(s) for DCM or other diseases affecting the striated muscle cannot be identified. Conversely, in adipose tissue defects, approximately 80% of cases carry a substitution of the p.Arg482 residue while 85% of mandibuloacral dysplasia cases are caused by a homozygous mutation at the p.527 residue and 77% of HGPS patients carry the c.1827C>T substitution within exon 11 [16]. Studies of cellular phenotypes associated with LMNA mutations DCM patients with LMNA mutations display highly variable cardiomyocyte phenotype.…”

Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics

“…From these, 17 variants (0.57±0.77, mean±SD) have varying probabilities of pathogenicity. These include variants in genes routinely screened with Sanger sequencing—that is, MYH7 : NM_000257.2: c.1178C>T,26–28 c.1231G>A,29–32 c.2002C>A, c.5135G>A, c.1987C>T, c.121G>A and MYBPC3 : NM_000256.3: c.2827C>T,33 c.3004C>T (twice), c.2864_2865del, MYL2 : NM_000432.3: c.37G>A34–37 and TPM1 : NM_000366.5: c.618A>G, but also in genes that are part of the additional genes in the NG cardiomyopathy panel—that is, SCN5A : NM_198056.2: c.3157G>A38 39, PRKAG2 : NM_016203.3: c.253C>T, TCAP : NM_003673.2: c.37_39del,40 41 CSRP3 : NM_003476.3: c.10T>C42 43, LMNA : NM_170707.2: c.1804G>A,44 45 DES : NM_001927.3: c.935A>C (table 4). Ten patients had a single variant, two patients had two variants each ( MYH7 : NM_000257.2: c.1178C>T combined with SCN5A : NM_198056.2: c.3157G>A, and MYBPC3 : NM_000256.3: c.3004C>T combined with LMNA : NM_170707.2: c.1804G>A), and one patient had three variants ( MYH7 : NM_000257.2: c.121G>A, MYBPC3 : NM_000256.3: c.3004C>T, and DES : NM_001927.3: c.935A>C).…”

Novel c.367_369del LMNA mutation manifesting as severe arrhythmias, dilated cardiomyopathy, and myopathy

“…15 Dilated cardiomyopathy and cardiac conduction abnormalities with a strong tendency toward sudden cardiac death were reported in missense mutations, 2,5,12,18,19 nonsense mutations, 20 splice site mutations, 3,14,19,21,22 duplication/in-frame insertions, 19 and deletions. [2][3][4]11,13,19,[23][24][25][26] Mutations in LMNA resulting in cardiac abnormalities are most frequently located in exon 3, 5,13,25-27 exon 1, [28][29][30] or in the splice-receptor sequence of intron 6. 22 Only a few patients carrying LMNA mutations in exon 2 were reported.…”