@article {3173183,
	title = {GNE myopathy: can homozygous asymptomatic subjects give a clue for the identification of protective factors?},
	journal = {Neuromuscul Disord},
	volume = {33},
	year = {2023},
	month = {2023 Oct},
	pages = {762-768},
	abstract = {<p>
	GNE myopathy is caused by bi allelic recessive mutations in the GNE gene. The largest identified cohort of GNE myopathy patients carries a homozygous mutation- M743T (the "Middle Eastern" mutation). More than 160 such patients in 67 families have been identified by us. Mean onset in this cohort is 30 years (range 17-48) with variable disease severity. However, we have identified two asymptomatic females, homozygous for M743T in two different families, both with affected siblings. The first showed no myopathy when examined at age 76 years. The second has no sign of disease at age 60 years. Since both agreed only for testing of blood, we performed exome and RNA sequencing of their blood and that of their affected siblings. Various filtering layers resulted in 2723 variant loci between symptomatic and asymptomatic individuals, representing 1364 genes. Among those, 39 genes are known to be involved in neuromuscular diseases, and only in two of them the variant is located in the proper exon coding region, resulting in a missense change. Surprisingly, only 27 genes were significantly differentially expressed between the asymptomatic and the GNE myopathy affected individuals, with three overexpressed genes overlapping between exome and RNA sequencing. Although unable to unravel robust candidate genes, mostly because of the very low number of asymptomatic individuals analyzed, and because of the tissue analyzed (blood and not muscle), this study resulted in relatively restricted potential candidate protective genes, emphasizing the power of using polarized phenotypes (completely asymptomatic vs clearly affected individuals) with the same genotype to unmask those genes which could be used as targets for disease course modifiers.
</p>
},
	keywords = {Aged, Distal Myopathies, Female, Humans, Middle Aged, Muscle, Skeletal, Muscular Diseases, Mutation, Protective Factors},
	issn = {1873-2364},
	doi = {10.1016/j.nmd.2023.08.013},
	author = {Mitrani-Rosenbaum, Stella and Attali, Ruben and Argov, Zohar}
}
