The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia

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Skeletal dysplasias (SD) refer to a complex group of rare genetic disorders affecting the growth and development of the skeleton. The identification of the molecular basis of a considerable number of SD has greatly expanded our knowledge of the ossification process. Among SD, spondylodysplastic dysplasia is a generic term describing different conditions characterized by severe vertebral abnormalities and distinct by additional specific features. Several entities within this group are well defined. However, a few cases remain unclassified, of which a novel autosomal recessive spondylometaphyseal dysplasia recently reported by Mégarbané et al. in two Lebanese families. Here, we identified MAGMAS as a candidate gene responsible for this severe SD. MAGMAS, also referred to as PAM16, is a mitochondria-associated protein, involved in pre-proteins import into mitochondria and essential for cell growth and development. We demonstrated that MAGMAS is expressed in bone and cartilage in early developmental stages underlining its specific role in skeletogenesis. We also give strong evidence of the deleterious effect of the identified mutation on the in-vivo activity of Magmas and the viability of yeast strains. Reporting deleterious MAGMAS mutation in a SD supports a key and specific role for this mitochondrial protein in ossification.

Vyšlo v časopise: The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004311
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004311

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