title: [North American Indian childhood cirrhosis (NAIC)].
abstract: North American Indian childhood cirrhosis is a distinct form of neonatal familial cholestasis. To date, it has only been described in aboriginal children from northwestern Quebec. The disease rapidly evolves into cirrhosis with early portal hypertension and bleeding from esophageal varices. Twelve of 36 children followed at l'Hôpital Ste-Justine since 1970 received a liver transplant. As of now, there are 17 living NAIC patients, 6 of whom had liver transplantation. We mapped NAIC to chromosome 16q22, and identified mutations in CIRH1A in patients. All are homozygous for the R565W mutation in cirhin, a WD40 repeat protein of unknown function. We showed that cirhin is a resident in the nucleolus. Cirhin interacts with Cirip, a functional, alternative splice variant of the HIVEP1 protein. Their interaction indicates synergistic action. The complete inactivation of mouse homolog, tex292 is likely embryonic lethal. The continued collaboration between patients, their families, clinicians and researchers that has helped to identify the disease gene and to develop a diagnostic test now focuses on finding a new treatment for this unique disease affecting First Nations children from Québec.
authors.affiliation: Services de Génétique Médicale et de Gastroentérologie, Hôpital Sainte Justine, Département de Pédiatrie, Université de Montréal, 3175, chemin de la Côte Sainte-Catherine, Montréal (Québec) H3T 1C5, Canada. andrea.richter@umontreal.ca
authors.forename: Andrea
authors.initials: A
authors.lastname: Richter
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
authors.forename: Andrée
authors.initials: A
authors.lastname: Rasquin
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002779:Cholestasis / Q000453:epidemiology / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004932:Esophageal and Gastric Varices / Q000209:etiology; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007198:Indians, North American / Q000235:genetics / Q000706:statistics & numerical data*; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000235:genetics; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D049452:Green Fluorescent Proteins; D004247:DNA