Duplication in the Microtubule-Actin Cross-linking Factor 1 gene causes a novel neuromuscular condition
Spectrins and plakins are important communicators linking cytoskeletal components to each other and to cellular junctions. Microtubule-actin cross-linking factor 1 (MACF1) belongs to the spectraplakin family and is involved in control of microtubule dynamics. Complete knock out of MACF1 in mice is associated with developmental retardation and embryonic lethality. Here we present a family with a novel neuromuscular condition. Genetic analyses show a heterozygous duplication resulting in reduced MACF1 gene product. The functional consequence is affected motility observed as periodic hypotonia, lax muscles and diminished motor skills, with heterogeneous presentation among the affected family members. To corroborate these findings we used RNA interference to knock down the VAB-10 locus containing the MACF1 homologue in C. elegans, and we could show that this also causes movement disturbances. These findings suggest that changes in the MACF1 gene is implicated in this neuromuscular condition, which is an important observation since MACF1 has not previously been associated with any human disease and thus presents a key to understanding the essential nature of this gene.
[…] The Oxford Gene Technology Syndrome Plus v.2 format was used for array-CGH analysis. Labelling and hybridization were done according to standard protocol from Oxford Gene Technology and scanning was performed on a Perkin Elmer Scanarray gX scanner at a resolution of 5 μm. Genepix Pro 6.1 was used for feature extraction and Cytosure Interpret software v3.4.3 was used for data analysis. […]