ATP7B variant spectrum in a French pediatric ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
ATP7B variant spectrum in a French pediatric Wilson disease cohort.
Author(s) :
Couchonnal, Eduardo [Auteur]
Hôpital Femme Mère Enfant [CHU - HCL] [HFME]
Bouchard, Sophie [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Damgaard Sandahl, Thomas [Auteur]
Aarhus University Hospital
Pagan, Cécile [Auteur]
Hospices Civils de Lyon [HCL]
Service de biochimie et biologie moléculaire
Lion-François, L. [Auteur]
Guillaud, O. [Auteur]
Habes, Dalila [Auteur]
Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre]
Debray, Dominique [Auteur]
Physiopathogénèse et Traitement des Maladies du Foie
Lamireau, Thierry [Auteur]
CHU Bordeaux
Broué, P. [Auteur]
Service de Gastroentérologie et pancréatologie [CHU Toulouse]
Fabre, A. [Auteur]
Hôpital de la Timone [CHU - APHM] [TIMONE]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Vanlemmens, C. [Auteur]
Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon]
Sobesky, R. [Auteur]
Centre Hépato-Biliaire [Hôpital Paul Brousse] [CHB]
Gottrand, fréderic [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)]
Bridoux-Henno, L. [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
Belmalih, A. [Auteur]
Poujois, A. [Auteur]
Brunet, A. S. [Auteur]
Lachaux, A. [Auteur]
Bost, M. [Auteur]
Hôpital Femme Mère Enfant [CHU - HCL] [HFME]
Bouchard, Sophie [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Damgaard Sandahl, Thomas [Auteur]
Aarhus University Hospital
Pagan, Cécile [Auteur]
Hospices Civils de Lyon [HCL]
Service de biochimie et biologie moléculaire
Lion-François, L. [Auteur]
Guillaud, O. [Auteur]
Habes, Dalila [Auteur]
Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre]
Debray, Dominique [Auteur]
Physiopathogénèse et Traitement des Maladies du Foie
Lamireau, Thierry [Auteur]
CHU Bordeaux
Broué, P. [Auteur]
Service de Gastroentérologie et pancréatologie [CHU Toulouse]
Fabre, A. [Auteur]
Hôpital de la Timone [CHU - APHM] [TIMONE]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Vanlemmens, C. [Auteur]
Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon]
Sobesky, R. [Auteur]
Centre Hépato-Biliaire [Hôpital Paul Brousse] [CHB]
Gottrand, fréderic [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)]
Bridoux-Henno, L. [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
Belmalih, A. [Auteur]
Poujois, A. [Auteur]
Brunet, A. S. [Auteur]
Lachaux, A. [Auteur]
Bost, M. [Auteur]
Journal title :
European Journal of Medical Genetics
Abbreviated title :
Eur J Med Genet
Pages :
104305
Publication date :
2021-08-18
ISSN :
1878-0849
English keyword(s) :
Wilson's disease
ATP7B
p.His1069Gln
Phenotype-genotype correlation
ATP7B
p.His1069Gln
Phenotype-genotype correlation
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-12T06:13:16Z
2024-02-28T15:00:07Z
2024-02-28T15:00:07Z
Files
- document
- Open access
- Pre-print
- Access the document