Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility - Aix-Marseille Université Access content directly
Journal Articles American Journal of Human Genetics Year : 2018

Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility

Ludmila Francescatto
  • Function : Author
Perciliz Tan
  • Function : Author
Cécile de Leusse
  • Function : Author
Yannis Duffourd
  • Function : Author
  • PersonId : 994654
Emmanuel Ecochard-Dugelay
  • Function : Author
Philippe Gauchez
  • Function : Author
Catherine Guettier-Bouttier
  • Function : Author
Mina Komuta
  • Function : Author
Raphaelle Maudinas
  • Function : Author
Karin Mazodier
  • Function : Author
Yves Rimet
  • Function : Author
Xavier Stephenne
  • Function : Author
Laurence Faivre
  • Function : Author
  • PersonId : 856301

Abstract

Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.

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Human genetics

Dates and versions

hal-01721495 , version 1 (02-03-2018)

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Clothilde Esteve, Ludmila Francescatto, Perciliz Tan, Aurélie Bourchany, Cécile de Leusse, et al.. Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility. American Journal of Human Genetics, 2018, 102 (3), pp.364 - 374. ⟨10.1016/j.ajhg.2018.01.009⟩. ⟨hal-01721495⟩
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