A New Mutation of Wilson's Disease P-Type ATPase Gene in a Patient with Cirrhosis and Coombs-Positive Hemolytic Anemia

Leggio, Lorenzo; Addolorato, Giovanni; Loudianos, Georgios; Abenavoli, Ludovico; Lepori, Maria Barbara; Vecchio, Fabio Maria; Rapaccini, Gian Ludovico; Virgiliis, Stefano De; Gasbarrini, Giovanni

doi:10.1007/s10620-006-3080-8

Cited by 6 publications

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References 34 publications

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“…In fact, hemolytic anemia is usually characterized by a Coombs-negative test in WD, and it can be related to chronic liver disease [Leggio et al, 2005] although a homozygous truncation of ATP7B at Arg1319 in a WD patient presenting Coombsnegative hemolytic anemia without liver failure has been described [Prella et al, 2001]. As regard to genotype, the T1288R mutation (exon 18) is a nonconservative aminoacidic substitution as it replaces a neutral polar aminoacid with basic residue in the ATP hinge region, the flexible loop connecting the ATP binding domain with the transmembrane segment (Tm) 7 [Leggio et al, 2006]. The delection described by Moller et al [2005] (exon 20) leads to a mutated protein product after Tm7 lacking Tm8 as well as the entire C-terminal cytoplasmatic tail.…”

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confidence: 99%

Genotype–phenotype correlation of the Wilson diseaseATP7B gene

Leggio¹,

Addolorato²,

Loudianos³

et al. 2006

Am. J. Med. Genet.

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confidence: 99%

Genotype–phenotype correlation of the Wilson diseaseATP7B gene

Leggio¹,

Addolorato²,

Loudianos³

et al. 2006

Am. J. Med. Genet.

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“…A new missense homozygote mutation (T1288R) in exon 18 of the ATP7B gene in a 30-year-old Caucasian Sicilian man with WD, presenting with liver cirrhosis, Kayser-Fleischer rings without neurological manifestations, and a good response to penicillamine, was recently discovered in our laboratory [10]. Moreover, a particular clinical feature of the patient was the presence of a Coombs-positive hemolytic anemia at the time of diagnosis, never before described in WD [10].…”

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confidence: 76%

“…Moreover, a particular clinical feature of the patient was the presence of a Coombs-positive hemolytic anemia at the time of diagnosis, never before described in WD [10].…”

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confidence: 81%

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Analysis of the T1288R Mutation of the Wilson Disease ATP7B Gene in Four Generations of a Family: Possible Genotype-Phenotype Correlation with Hepatic Onset

et al. 2007

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Wilson disease, an autosomal recessive disorder due to mutations of the ATP7B gene, is characterized by copper accumulation and toxicity in the liver and subsequently in other organs, mainly the brain and cornea. A new missense mutation (T1288R) of the ATP7B gene has recently been discovered in a Wilson disease patient in our laboratory. The aim of the present study was to analyze clinical and genetic features of more generations of the family of the patient in which the new mutation T1288R was discovered. A total of 19 subjects were studied; in particular, four generations of the patient's family were analyzed. The ATP7B gene was analyzed by single-strand conformational polymorphism followed by direct sequencing. Two brothers presented a clinical diagnosis of Wilson disease with an hepatic phenotype and a genotype characterized by the homozygotic mutation T1288R. The heterozygotic mutation T1288R was found in seven subjects belonging to all four generations. The present study represents the first screening for a Wilson disease mutation through four generations of a nonconsanguineous family. All the patients with the homozygotic T1288R mutation in the present pedigree presented an hepatic phenotype without a neurological presentation. Consequently, a genotype-phenotype correlation could be hypothesized, although further studies are necessary to clarify this topic.

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