1. Calpainopathy: Description of a Novel Mutation and Clinical Presentation with Early Severe Contractures
- Author
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Julián Fernandez, Víctor Villareal, Oscar M. Vidal, Sergio Landires, Samuel Martínez, Iván Landires, Giovanni Apraez-Ippolito, Virginia Núñez-Samudio, Mauricio Arcos-Burgos, Mauricio Arcos-Holzinger, Fernando Córdoba, Cesar Sarria, and Jorge I. Vélez
- Subjects
0301 basic medicine ,Male ,Pathology ,clinical presentation ,Muscle Proteins ,medicine.disease_cause ,Muscular Dystrophies ,Bilateral talipes equinovarus ,Exon ,0302 clinical medicine ,deletion ,Muscular dystrophy ,Child ,Genetics (clinical) ,Sequence Deletion ,Mutation ,biology ,Calpain ,Homozygote ,Exons ,calpainopathy ,Pedigree ,founder effect ,Phenotype ,Female ,Emery–Dreifuss-like syndrome ,Adult ,medicine.medical_specialty ,Clubfoot ,lcsh:QH426-470 ,Adolescent ,Amerindian populations ,Article ,03 medical and health sciences ,Genetics ,medicine ,calpain gene ,Humans ,Family ,Muscle contracture ,business.industry ,medicine.disease ,calpain 3-related, limb-girdle muscular dystrophy type r1 ,lcsh:Genetics ,030104 developmental biology ,Muscular Dystrophies, Limb-Girdle ,biology.protein ,novel mutation ,business ,030217 neurology & neurosurgery ,Founder effect - Abstract
Presented here are five members of a family that was ascertained from an isolated, consanguineous, indigenous Amerindian community in Colombia that was affected with calpain 3-related, limb-girdle muscular dystrophy type R1. These patients are homozygous for a unique and novel deletion of four bases (TGCC) in exon 3 of the calpain 3 gene (CAPN3) (NM_000070.2, NP_000061.1) (g.409_412del). The mutation site occurs at the CysPc protein domain, triggering a modified truncated protein structure and affecting motifs within the calpain-like thiol protease family (peptidase family C2) region. The patients reported here developed a very severe phenotype with primary contractures, spinal rigidity in the early stages of the disease, and bilateral talipes equinovarus (clubfoot) in the most affected patients who had the selective involvement of their extremities&rsquo, distal muscles in a way that resembled Emery&ndash, Dreifuss syndrome. We recommend mandatory screening for calpainopathy in all patients with an Emery&ndash, Dreifuss-like syndrome or those presenting a non-congenital illness with primary contractures and who, because of other data, are suspected of having muscular dystrophy.
- Published
- 2020