Table 1.

Clinical features of Laminopathy mutations on tail region of LMNA gene

MutationMutation statusClinical featuresReferencesAffinity to BAF (Samson et al., 2018)
Q432X Heterozygous DCM, CCD, asymptomatic Møller et al. (2009)  ND 
R435C Heterozygous DCM, CCD, asymptomatic Vytopil et al. (2003),
Madej-Pilarczyk et al. (2009)  
− 
Homozygous progeroid syndrome, myopathy, RD 
R453W Heterozygous EDMD, LGMD, CCD, AF, asymptomatic Bonne et al. (1999),
Bonne et al. (2000),
di Barletta et al. (2000),
Brown et al. (2001),
Colomer et al. (2002),
Vytopil et al. (2003),
Muchir et al. (2004),
Golzio et al. (2007),
Mitsuhashi et al. (2010)  
++ 
R471C Heterozygous progeroid syndrome, HCM, myopathy, DCM, CCD, asymptomatic Cao and Heqele (2003),
Zirn et al. (2008),
Rudbeck-Resdal et al. (2019),
Rupp et al. (2019)  
Homozygous MAD, EDMD 
R482W Heterozygous FPLD, diabetes, IR, GI, dyslipidemia, NASH, PHA, euthyroid goiter, polycystic ovaries, retinopathy, extrapyramidal syndrome, myopathy, LGMD, DCM, CCD, asymptomatic Shackleton et al. (2000),
Hegele et al. (2000),
Speckman et al. (2000),
Vigouroux et al. (2000),
Vantyghem et al. (2004),
Vantyghem et al. (2007),
Béréziat et al. (2011),
Panikkath et al. (2016),
Akinci et al. (2017)  
++ 
R527H Heterozygous MAD, myopathy, asymptomatic Novelli et al. (2002),
Simha et al. (2003),
Shen et al. (2003),
Lombardi et al. (2007)  
+/− 
Homozygous MAD 
A529V Heterozygous diabetes, asymptomatic Garg et al. (2005),
Ozer et al. (2016)  
Homozygous MAD 
K542N Heterozygous asymptomatic Plasilova et al. (2004)  +/− 
Homozygous progeroid syndrome 
MutationMutation statusClinical featuresReferencesAffinity to BAF (Samson et al., 2018)
Q432X Heterozygous DCM, CCD, asymptomatic Møller et al. (2009)  ND 
R435C Heterozygous DCM, CCD, asymptomatic Vytopil et al. (2003),
Madej-Pilarczyk et al. (2009)  
− 
Homozygous progeroid syndrome, myopathy, RD 
R453W Heterozygous EDMD, LGMD, CCD, AF, asymptomatic Bonne et al. (1999),
Bonne et al. (2000),
di Barletta et al. (2000),
Brown et al. (2001),
Colomer et al. (2002),
Vytopil et al. (2003),
Muchir et al. (2004),
Golzio et al. (2007),
Mitsuhashi et al. (2010)  
++ 
R471C Heterozygous progeroid syndrome, HCM, myopathy, DCM, CCD, asymptomatic Cao and Heqele (2003),
Zirn et al. (2008),
Rudbeck-Resdal et al. (2019),
Rupp et al. (2019)  
Homozygous MAD, EDMD 
R482W Heterozygous FPLD, diabetes, IR, GI, dyslipidemia, NASH, PHA, euthyroid goiter, polycystic ovaries, retinopathy, extrapyramidal syndrome, myopathy, LGMD, DCM, CCD, asymptomatic Shackleton et al. (2000),
Hegele et al. (2000),
Speckman et al. (2000),
Vigouroux et al. (2000),
Vantyghem et al. (2004),
Vantyghem et al. (2007),
Béréziat et al. (2011),
Panikkath et al. (2016),
Akinci et al. (2017)  
++ 
R527H Heterozygous MAD, myopathy, asymptomatic Novelli et al. (2002),
Simha et al. (2003),
Shen et al. (2003),
Lombardi et al. (2007)  
+/− 
Homozygous MAD 
A529V Heterozygous diabetes, asymptomatic Garg et al. (2005),
Ozer et al. (2016)  
Homozygous MAD 
K542N Heterozygous asymptomatic Plasilova et al. (2004)  +/− 
Homozygous progeroid syndrome 

See the 3D structure in Fig. 5 D for the mutated amino acids shown in table. ++, No defects on in vitro binding affinity to BAF; +, Weak binding affinity to BAF; +/−, No measureable affinity; −, No detected binding. All accumulation kinetics are shown in Fig. 5 E and images are in Fig. S4 A. DCM, dilated cardiomyopathy; CCD, cardiac conduction disturbance; RD, restrictive dermopathy; EDMD, Emery-Dreifuss muscular dystrophy; LGMD, limb-girdle muscular dystrophy; AF, atrial fibrillation; HCM, hypertrophic cardiomyopathy; MAD, mandibuloacral dysplasia; FPLD, familial partial lipodystrophy; IR, severe insulin resistance; GI, glucose intolerance; NASH, nonalcoholic steatohepatitis; PHA, primary hyperaldosteronism.

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