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ATP7B variant spectrum in a French pediatric Wilson disease cohort.
Couchonnal, Eduardo; Bouchard, Sophie; Sandahl, Thomas Damgaard; Pagan, Cecile; Lion-François, Laurence; Guillaud, Olivier; Habes, Dalila; Debray, Dominique; Lamireau, Thierry; Broué, Pierre; Fabre, Alexandre; Vanlemmens, Claire; Sobesky, Rodolphe; Gottrand, Frederic; Bridoux-Henno, Laure; Belmalih, Abdelouahed; Poujois, Aurelia; Brunet, Anne Sophie; Lachaux, Alain; Bost, Muriel.
Afiliación
  • Couchonnal E; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany. Electronic address: eduardo.couchonnal-bedoya@chu-
  • Bouchard S; Claude Bernard Lyon 1 University Lyon, France.
  • Sandahl TD; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark.
  • Pagan C; Department of Biochemistry and Molecular Biology, LBMMS, Hospices Civils de Lyon, France.
  • Lion-François L; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany.
  • Guillaud O; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany.
  • Habes D; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Biliary Atresia and Genetic Cholestasis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-B
  • Debray D; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Inserm U1193, Hepatinov, University of Paris Saclay, Orsay, France.
  • Lamireau T; Children's Hospital, Paediatric Gastroenterology Unit, Bordeaux, France.
  • Broué P; Children University Hospital, Metabolic Disease Department, Toulouse, France.
  • Fabre A; APH, Timone Enfant, Service de Pédiatrie Multidisciplinaire, Marseille, France; Aix Marseille Univ, INSERM, MMG, Marseille, France.
  • Vanlemmens C; University Hospital of Besancon, Paediatric Gastroenterology Unit, Besacon, France.
  • Sobesky R; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Paul Brousse Hospital, Hepatobiliary Centre, Hepatobiliary Centre, France.
  • Gottrand F; Univ- Lille, CHU Lille, UMR1286 Department of Pediatric Gastroenterology Hepatology and Nutrition, Lille, France.
  • Bridoux-Henno L; CHU Rennes, Department of Pediatric Gastroenterology, Rennes, France.
  • Belmalih A; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany.
  • Poujois A; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; French National Rare Disease Reference Centre "Wilson's Disease and Other Copper-related Rare Diseases", Rothschild Foundation Hospital, Neurology Department, Paris, France.
  • Brunet AS; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France.
  • Lachaux A; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Claude Bernard Lyon 1 University Lyon, France.
  • Bost M; Hospices Civils de Lyon. National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Germany; Department of Biochemistry and Molecular Biology,
Eur J Med Genet ; 64(10): 104305, 2021 Oct.
Article en En | MEDLINE | ID: mdl-34400371
BACKGROUND/AIM: The spectrum of ATP7B variants varies significantly according to geographic distribution, and there is insufficient data on the variants observed in the French population. METHODS: Clinical data of 113 children included in the French WD national registry were gathered from March 01, 1995 to July 01, 2020. Data included epidemiological, clinical, laboratory, genetics. RESULTS: Diagnosis was made at a mean age of 11.0 ± 4.1 years (range 1-18 years). At diagnosis, 91 patients (79.8 %) had hepatic manifestations, 18 (15.8 %) presented neurological manifestations, and 4 patients (3.5 %) were asymptomatic. Only 29 patients (25 %) were homozygous for a variant. We have found a total of 102 different variants including 14 novel variants. Recurrent variant p.His1069Gln was the most prevalent, n = 31 alleles (14,2%), with only seven homozygous; in contrast 55% of variants are identified in only one family. 45% were truncating variants. In respect of mutated exon, the three most prevalent were exon 14 (16.5%), exon 8 (13.8%), and exon 3 (11.5%). When considering patients with two Nonsense / Frameshift variants as a group and those with two Missense variants, we found significantly lower ceruloplasmin for the former: 2.8 ± 0.7 mg/dl vs 8.4 ± 5mg/dl (p<0.05). CONCLUSION: p.His1069Gln is the most frequent variant (14,2%) and exons 14, 8, and 2 of the ATP7B gene account for 41.7% of total variants. However, there is significant heterogeneity in the French population concerning the other ATP7B variants. Nonsense / Frameshift variants were associated with lower ceruloplasmin levels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / ATPasas Transportadoras de Cobre / Degeneración Hepatolenticular Tipo de estudio: Risk_factors_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / ATPasas Transportadoras de Cobre / Degeneración Hepatolenticular Tipo de estudio: Risk_factors_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Eur J Med Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos