Abstract

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 01/03/1995 to 01/07/2020. 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.