@article{fdi:010070378,
  title = {{E}xome sequencing identifies two variants of the alkylglycerol monooxygenase gene as a cause of relapses in visceral leishmaniasis in children, in {S}udan},
  author = {{M}arquet, {S}. and {B}ucheton, {B}runo and {R}eymond, {C}. and {A}rgiro, {L}. and {E}l-{S}afi, {S}. {H}. and {K}heir, {M}. {M}. and {D}esvignes, {J}. {P}. and {B}eroud, {C}. and {M}ergani, {A}. and {H}ammad, {A}. and {D}essein, {A}. {J}.},
  editor = {},
  language = {{ENG}},
  abstract = {{V}isceral leishmaniasis (kala-azar, {KA}) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly, and lymphadenopathy. {D}uring an outbreak of {KA} in {B}abar {E}l {F}ugara ({S}udan), 5.7% of cured patients displayed relapses, with familial clustering in half the cases. {W}e performed whole-exome sequencing on 10 relapsing individuals and 11 controls from 5 nuclear families. {R}are homozygous and compound-heterozygous nonsense (c.1213{C} > {T}, rs139309795, p.{A}rg405*) and missense (c.701{A} > {G}, rs143439626, p.{L}ys234{A}rg) mutations of the alkylglycerol monooxygenase ({AGMO}) gene were associated with {KA} relapse in 3 families. {S}equencing in additional family members confirmed the segregation of these mutations with relapse and revealed an autosomal dominant mode of transmission. {T}hese mutations were detected heterozygous in 2 subjects among 100 unrelated individuals with {KA} who never relapsed after cure, suggesting incomplete penetrance of {AGMO} deficiency. {AGMO} is expressed in hematopoietic cells, and is strongly expressed in the liver. {AGMO} modulates {PAF} production by mouse macrophages, suggesting that it may act through the {PAF}/{PAF} receptor pathway previously shown to have anti-{L}eishmania activity. {T}his is the first demonstration that relapses after a first episode of {KA} are due to differences in human genetic susceptibility and not to modifications of parasite pathogenicity.},
  keywords = {{AGMO} ; exome sequencing ; genetic variants ; haploinsufficiency ; {K}ala-azar ; relapse ; {SOUDAN}},
  booktitle = {},
  journal = {{J}ournal of {I}nfectious {D}iseases},
  volume = {216},
  numero = {1},
  pages = {22--28},
  ISSN = {0022-1899},
  year = {2017},
  DOI = {10.1093/infdis/jix277},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070378},
}