SRX Biology

SRX Biology / 2010 / Article

Research Article | Open Access

Volume 2010 |Article ID 301679 |

Nicola Carboni, Matteo Floris, Maria Valentini, Giovanni Marrosu, Eleonora Cocco, Maria Antonietta Maioli, Elisabetta Solla, Anna Mateddu, Marco Mura, Maria Giovanna Marrosu, "A Novel Mutation in Lamin A/C Gene: Phenotype and Consequences on the Protein Structure and Flexibility", SRX Biology, vol. 2010, Article ID 301679, 7 pages, 2010.

A Novel Mutation in Lamin A/C Gene: Phenotype and Consequences on the Protein Structure and Flexibility

Received21 Oct 2009
Revised07 Jan 2010
Accepted01 Feb 2010
Published15 Mar 2010


Laminopathies are a heterogeneous group of LMNA gene alteration-related disorders including muscular dystrophies, peripheral neuropathies, progeria, lipodystrophies, mandibuloacral dysplasia and restrictive dermopathy. We recently identified a family displaying mild skeletal muscle compromise and contractures and complaining of cardiac symptoms associated to a novel mutation consisting in c.388 G/T exon 2 LMNA gene substitution. The aim of the study was to assess the pathogenic effect of this mutation by means of computational experiments. The c.388 G/T mutation is a missense mutation causing the substitution of the amino acid Alanine with Serine in position 130 of the protein sequence of the coiled-coil region of Lamin A rod domain. Computational predictions and molecular dynamic simulation of lamin filaments revealed a 50% reduction in the probability of the sequence adopting a coiled-coil conformation. The present study provides a feasible explanation for the potential pathogenic effect of the novel c.388 G/T exon 2 LMNA gene mutation. The simulation revealed how the mutation alters the flexibility of lamin filaments and likely determines an impairment in the constitution of the coiled-coil structure.


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Copyright © 2010 Nicola Carboni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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