Duplication in the Microtubule-Actin Cross-linking Factor 1 gene causes a novel neuromuscular condition

• DOI: 10.1038/srep05180
• Publication Date: 2014-06-05T09:06:52Z
• Authors: Louise H. Jørgensen; Mai-Britt Mosbech; Nils J. Færgeman; Jesper Graakjaer; Søren V. Jacobsen; Henrik D. Schrøder
• Keywords: Male; 0301 basic medicine; Comparative Genomic Hybridization; Blotting, Western; Microfilament Proteins; Apoptosis; Neuromuscular Diseases; Microtubules; Article; Pedigree; Animals, Genetically Modified; Immunoenzyme Techniques; Mice; 03 medical and health sciences; Gene Duplication; Animals; Humans; Female; RNA Interference; Caenorhabditis elegans; Child; Cells, Cultured; Cell Proliferation

Spectrins and plakins are important communicators linking cytoskeletal components to each other cellular junctions. Microtubule-actin cross-linking factor 1 (MACF1) belongs the spectraplakin family is involved in control of microtubule dynamics. Complete knock out MACF1 mice associated with developmental retardation embryonic lethality. Here we present a novel neuromuscular condition. Genetic analyses show heterozygous duplication resulting reduced gene product. The functional consequence affected motility observed as periodic hypotonia, lax muscles diminished motor skills, heterogeneous presentation among members. To corroborate these findings used RNA interference down VAB-10 locus containing homologue C. elegans could that this also causes movement disturbances. These suggest changes implicated condition, which an observation since has not previously been any human disease thus presents key understanding essential nature gene.