Issue |
Med Sci (Paris)
Volume 23, Number 11, Novembre 2007
|
|
---|---|---|
Page(s) | 1002 - 1007 | |
Section | M/S revues | |
DOI | https://doi.org/10.1051/medsci/200723111002 | |
Published online | 15 November 2007 |
La cirrhose amérindienne infantile
North American Indian childhood cirrhosis (NAIC)
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
Nous décrivons ici comment une maladie survenant uniquement chez les enfants amérindiens du Nord-Ouest du Québec a pu être diagnostiquée et le gène responsable détecté. Il s’agit d’une cholestase néonatale évoluant irrémédiablement vers la cirrhose et pour laquelle la transplantation hépatique représente actuellement la seule solution thérapeutique. La maladie est transmise de façon autosomique récessive et le taux des porteurs du gène muté est de 10 % dans les communautés concernées. Dans tous les cas détectés à ce jour, la mutation provoque la substitution d’un acide aminé (R565W) dans la protéine cirhin, produit du locus CIRH1A.
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.
© 2007 médecine/sciences - Inserm / SRMS
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