1.
J Pediatr Gastroenterol Nutr
; 68(5): e85, 2019 May.
Artigo
em Inglês
| MEDLINE
| ID: mdl-29727438
Assuntos
Carcinoma Hepatocelular/congênito , Colestase/congênito , Deleção de Genes , Fator 1-beta Nuclear de Hepatócito/genética , Neoplasias Hepáticas/congênito , Carcinoma Hepatocelular/diagnóstico , Colestase/diagnóstico , Células Germinativas , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/diagnóstico , Masculino , Ultrassonografia Pré-Natal
2.
Am J Hum Genet
; 102(3): 364-374, 2018 03 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-29429573
RESUMO
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.