6533b872fe1ef96bd12d2fe1

RESEARCH PRODUCT

Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations in UNC45A

C. Thauvin-robinetHery GNicholas KatsanisAurélie FabreEcochard-dugelay EDe Leusse CY. RimetAnge-line BruelDelarue AP. GauchezXavier StéphennePatrice BourgeoisR. MaudinasLudmila FrancescattoCéline Brochier-armanetYannis DuffourdArnaud BlanchardMarinier ELaurence FaivreOlivier GouletPerciliz L. TanCaroline LacosteJ. SarlesJean-pierre HugotClothilde EsteveK. MazodierSabine SigaudyEmmanuel GonzalesAurélie BourchanyNicolas LévyC. Guettier-bouttierCatherine BadensFrédéric HuetJean-baptiste RivièreJulien ThevenonBertrand RoquelaureMina Komuta

subject

Candidate geneCholestasisIn vivoConcomitantMyosinImmunologymedicineCancer researchBiologymedicine.diseaseGeneLoss functionExome sequencing

description

AbstractDespite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. 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.

yearjournalcountryeditionlanguage
2017-10-26
10.1101/208942http://dx.doi.org/10.1101/208942