TY - JOUR
T1 - Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene
AU - Garg, Abhimanyu
AU - Speckman, Rebecca A.
AU - Bowcock, Anne M.
N1 - Funding Information:
Supported in part by the National Institutes of Health grants R01-DK54387 and M01-RR00633, as well as grants from the Moss Heart Foundation and the Southwest Medical Foundation.
PY - 2002
Y1 - 2002
N2 - PURPOSE: Mutations in different domains of the LMNA (lamin A/C) gene encoding nuclear envelope proteins lamin A and lamin C cause familial partial lipodystrophy (Dunnigan variety), dilated cardiomyopathy, and autosomal dominant forms of Emery-Dreifuss and limb-girdle muscular dystrophies. The objective of this study was to evaluate LMNA variants in two families with familial partial lipodystrophy (Dunnigan variety) who also had cardiac conduction system defects and other manifestations related to cardiomyopathy. METHODS: We performed mutational analysis of the lamin A/C gene in affected and unaffected subjects by deoxyribonucleic acid sequencing of the exons. RESULTS: Two novel missense mutations were identified in exon 1 of the lamin A/C gene. One mutation, R28W (CGG→TGG), affected the amino-terminal head domain, and the other, R62G (CGC→GGC), affected the α-helical rod domain. Affected subjects from both families had an increased prevalence of cardiac manifestations, such as atrioventricular conduction defects, atrial fibrillation, and heart failure due to ventricular dilatation, as well as pacemaker implantation. The proband from one of the families also had proximal muscle weakness. CONCLUSION: Novel genetic defects in the LMNA gene in two families with the Dunnigan variety of familial partial lipodystrophy, cardiac conduction system defects, and other manifestations related to cardiomyopathy suggest the occurrence of a multisystem dystrophy syndrome due to LMNA mutations.
AB - PURPOSE: Mutations in different domains of the LMNA (lamin A/C) gene encoding nuclear envelope proteins lamin A and lamin C cause familial partial lipodystrophy (Dunnigan variety), dilated cardiomyopathy, and autosomal dominant forms of Emery-Dreifuss and limb-girdle muscular dystrophies. The objective of this study was to evaluate LMNA variants in two families with familial partial lipodystrophy (Dunnigan variety) who also had cardiac conduction system defects and other manifestations related to cardiomyopathy. METHODS: We performed mutational analysis of the lamin A/C gene in affected and unaffected subjects by deoxyribonucleic acid sequencing of the exons. RESULTS: Two novel missense mutations were identified in exon 1 of the lamin A/C gene. One mutation, R28W (CGG→TGG), affected the amino-terminal head domain, and the other, R62G (CGC→GGC), affected the α-helical rod domain. Affected subjects from both families had an increased prevalence of cardiac manifestations, such as atrioventricular conduction defects, atrial fibrillation, and heart failure due to ventricular dilatation, as well as pacemaker implantation. The proband from one of the families also had proximal muscle weakness. CONCLUSION: Novel genetic defects in the LMNA gene in two families with the Dunnigan variety of familial partial lipodystrophy, cardiac conduction system defects, and other manifestations related to cardiomyopathy suggest the occurrence of a multisystem dystrophy syndrome due to LMNA mutations.
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U2 - 10.1016/S0002-9343(02)01070-7
DO - 10.1016/S0002-9343(02)01070-7
M3 - Article
C2 - 12015247
AN - SCOPUS:0036098280
SN - 0002-9343
VL - 112
SP - 549
EP - 555
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 7
ER -