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Article Dans Une Revue European Journal of Medical Genetics Année : 2021

ATP7B variant spectrum in a French pediatric Wilson disease cohort

Eduardo Couchonnal
  • Fonction : Auteur
Sophie Bouchard
  • Fonction : Auteur
Thomas Damgaard Sandahl
  • Fonction : Auteur
Cecile Pagan
  • Fonction : Auteur
Laurence Lion-Francois
  • Fonction : Auteur
Olivier Guillaud
  • Fonction : Auteur
Dalila Habes
  • Fonction : Auteur
Dominique Debray
  • Fonction : Auteur
Thierry Lamireau
Pierre Broue
  • Fonction : Auteur
Alexandre Fabre
  • Fonction : Auteur
Claire Vanlemmens
  • Fonction : Auteur
Rodolphe Sobesky
  • Fonction : Auteur
Laure Bridoux-Henno
  • Fonction : Auteur
Abdelouahed Belmalih
  • Fonction : Auteur
Aurelia Poujois
  • Fonction : Auteur
Anne Sophie Brunet
  • Fonction : Auteur
Alain Lachaux
  • Fonction : Auteur
  • PersonId : 907892
Muriel Bost
  • Fonction : Auteur

Résumé

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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hal-03468275 , version 1 (22-08-2023)

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Eduardo Couchonnal, Sophie Bouchard, Thomas Damgaard Sandahl, Cecile Pagan, Laurence Lion-Francois, et al.. ATP7B variant spectrum in a French pediatric Wilson disease cohort. European Journal of Medical Genetics, 2021, 64 (10), pp.104305. ⟨10.1016/j.ejmg.2021.104305⟩. ⟨hal-03468275⟩

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