The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis.
OBJECTIVE
Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype.


METHODS
Genotyping results in 70 Dutch patients were related to clinical presentation. Subsequently a meta-analysis for genotype-phenotype correlation was performed on all patients available from literature, combined with the current Dutch group, a total of 577 patients.


RESULTS
The Dutch patients homozygous or heterozygous for the H1069Q mutation presented more frequently with neurologic disease (63% and 43% vs. 15%), and at a later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q mutation. In the meta-analysis the odds-ratio for neurologic presentation in homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95% CI 2.01-6.09) and 2.13 (95% CI 1.18-3.83), respectively. Age at presentation was 21.1, 19.2 and 16.5 years, respectively, corresponding to a weighted mean difference (WMD) of 4.41 (95% CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients and 6.68 (95% CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients.


CONCLUSIONS
Our results indicate that the H1069Q mutation is associated with a late and neurologic presentation.
Stapelbroek
Janneke M
JM
Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.
Bollen
Casper W
CW
van Amstel
Johannes K Ploos
JK
van Erpecum
Karel J
KJ
van Hattum
Jan
J
van den Berg
Leonard H
LH
Klomp
Leo W J
LW
Houwen
Roderick H J
RH
D000251:Adenosine Triphosphatases / Q000235:genetics*; D017668:Age of Onset; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D009420:Nervous System / Q000503:physiopathology; D010641:Phenotype; D017354:Point Mutation
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases