[HTML][HTML] The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia

C Mehawej, A Delahodde, L Legeai-Mallet… - PLoS …, 2014 - journals.plos.org
C Mehawej, A Delahodde, L Legeai-Mallet, V Delague, N Kaci, JP Desvignes, Z Kibar…
PLoS genetics, 2014journals.plos.org
Impairment of the tightly regulated ossification process leads to a wide range of skeletal
dysplasias and deciphering their molecular bases has contributed to the understanding of
this complex process. Here, we report a homozygous mutation in the mitochondria-
associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS) in
a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16
(presequence translocase-associated motor 16), is a mitochondria-associated protein …
Impairment of the tightly regulated ossification process leads to a wide range of skeletal dysplasias and deciphering their molecular bases has contributed to the understanding of this complex process. Here, we report a homozygous mutation in the mitochondria-associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS) in a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16 (presequence translocase-associated motor 16), is a mitochondria-associated protein involved in preprotein translocation into the matrix. We show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein. We further demonstrate that the mutation described here confers to yeast strains a temperature-sensitive phenotype, impairs the import of mitochondrial matrix pre-proteins and induces cell death. The finding of deleterious MAGMAS mutations in an early lethal skeletal dysplasia supports a key role for this mitochondrial protein in the ossification process.
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