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.
Assuntos
Osso e Ossos/patologia , Colestase/genética , Diarreia/genética , Perda Auditiva/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação com Perda de Função/genética , Adolescente , Animais , Pré-Escolar , Diarreia/fisiopatologia , Família , Feminino , Fibroblastos/patologia , Motilidade Gastrointestinal , Humanos , Recém-Nascido , Linfócitos/patologia , Masculino , Linhagem , Fenótipo , Síndrome , Adulto Jovem , Peixe-ZebraAssuntos
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-NatalRESUMO
OBJECTIVE: The aim of this study was to describe the quality of life (QoL) of children with a chronic illness treated in a tertiary multidisciplinary pediatric department in comparison with the general population. STUDY DESIGN: A cross-sectional study was conducted in the tertiary multidisciplinary (nephrology, hepatogastroenterology, endocrinology, diabetology, transplantation) pediatric department of Timone Hospital in Marseille, France. Patients 8-17 years of age with a chronic disease were included during regular follow-up appointments. Medical and sociodemographic variables were obtained from medical records. Self-reported QoL was assessed using the VSPA (Vécu et Santé Perçu de l'Adolescent) questionnaire and parent-reported QoL was assessed using the VSPA questionnaire for parents. RESULTS: A total of 244 patients were included. Overall QoL did not differ significantly from that of the general population. Adolescent patients' self-reported QoL scores were lower than those of the general population in the domains of physical health and leisure, and parents reported QoL scores for adolescent patients lower than those of the general population for self-esteem and physical health. Adolescents' self-reported QoL scores were higher than in the general population for relationships with parents, healthcare professionals, and teachers as well as for school achievement. Parents also reported higher QoL scores in these areas for their children. CONCLUSION: Children and adolescents with a variety of chronic diseases had similar overall QoL scores to the general population but with different QoL profiles; their scores in some domains were higher than those of the general population.