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Abstract Background: Wilson’s disease is characterized by the toxic accumulation of copper in the liver, brain, cornea and other organs. It is caused by both impaired excretion via the bile and impaired incorporation of copper into ceruloplasmin in the liver. The Wilson’s disease gene (ATP7B) has been cloned as a putative copper-transporting P-type ATPase gene. We therefore analysed mutations of ATP7B in Japanese patients with Wilson’s disease. Methods: Twenty-three Japanese patients with Wilson’s disease were investigated. In all patients, the ATP7B coding sequence, including exon-intron junctions, was analysed by restriction endonuclease digestion, mutation detected enhancement gel electrophoresis and/or direct sequencing analysis of amplified fragments. Results: Thirteen mutations were identified, including seven missense mutations, four deletions, one insertion and one exon skipping in the coding region. The most common mutations were 2874deletion(del)C in exon 13 and arginine (Arg)778 leucine (Leu) in exon 8. Discussion: None of the observed mutations, except for 2302insertion(ins)C, have been previously detected in either European or North American patients. We conclude that the mutation spectrum of Wilson’s disease may thus indicate a population-dependent pattern. Based on the population-dependent manner of the occurrence of ATP7B gene mutations, it may be possible to establish a molecular diagnosis system. A molecular diagnosis system is considered to be very effective for making a definitive diagnosis in very young patients and for also detecting carriers. [ABSTRACT FROM AUTHOR]

We compared the bronchodilator response to salbutamol (albuterol) delivered by a compressed air nebulizer through a mouthpiece and via a facemask in 18 asthmatic children, to determine the most appropriate delivery method. Patients using a mouthpiece had significantly better mean percent increases in forced expiratory volume in 1 sec (FEV[sub 1]) and in forced vital capacity (FVC) than those using a facemask 30 min after inhalation (FEV[sub 1]: 56.4 ± 32.6% vs. 28.9 ± 19.1%, FVC: 34.4 ± 26.4% vs. 7.5 ± 14.9%, respectively). Nebulized therapy plays an important role in the management of bronchial asthma in children and should be delivered by a mouthpiece whenever possible in cases of exacerbated asthma. [ABSTRACT FROM AUTHOR]

We investigated two families with Wilson disease in which siblings showed different clinical phenotypes and different ages at onset. In Family 1, the second and fourth male children demonstrated onset of the neurological type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In Family 2, the second male child showed neurological symptoms at 32 years of age and was diagnosed as having the hepatoneurological type of Wilson disease; then the 35-year-old first female child was found to have the hepatic type by familial screening. We performed mutation analysis of the ATP7B gene for these patients, and found that the mutation was a compound heterozygote in both families. Previous reports of siblings with Wilson disease have shown an identical clinical phenotype and similar ages at onset. In addition, hepatic-type cases generally occur at lower ages compared with the neurological type. In the present investigation, however, younger patients showed neurological symptoms earlier than their older siblings, and clinical phenotypes differed among siblings in both families. These cases appear to be rare. Individual differences in copper accumulation in hepatic cells and intolerance to copper toxicity might be the reason for this phenomenon. Furthermore, there might be a difference in the dominance of the allele expressing ATP7B protein among these cases, resulting in different clinical phenotypes, because all patients of both families were found to be compound heterozygotes.