High frequency of the c.3207C&gt;A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson’s disease

Kučinskas, Laimutis; Jeroch, Jolanta; Vitkauskienė, Astra; Sakalauskas, Raimundas; Petrenkienė, Vitalija; Kučinskas, Vaidutis; Naginienė, Rima; Schmidt, H; Kupčinskas, Limas

doi:10.3748/wjg.14.5876

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…Although none of the WD mutations are predominant, several mutations show higher frequency in different world populations (Ferenci 2006). The best characterized H1069Q mutation is a prevalent mutation in Caucasian population of European origin (Vrabelova et al 2005), including Lithuanian (Kucinskas et al 2008), Czech (Vrabelova et al 2005) Hungarian (Folhoffer et al 2007), German (Huster et al 2004) and other groups. In contrast, the R778L mutation is predominant among Korean (Kusuda et al 2000; Park et al 2009), Chinese (Mak et al 2008), and Japanese (Kusuda et al 2000) patients.…”

Section: Phenotypic Variability and A Lack Of Genotype-phenotype Corrmentioning

confidence: 99%

Systems biology approach to Wilson’s disease

2011

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Wilson’s disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder.

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Section: Phenotypic Variability and A Lack Of Genotype-phenotype Corrmentioning

confidence: 99%

Systems biology approach to Wilson’s disease

2011

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“…However, variability even within the same families carrying the same genotype exists. The substitution mutation c.3207C>A (p.H1069Q) is identified more commonly in adult patients with neuropsychiatric manifestations, but can also occur in children with acute liver failure [45]. However, very little is known with regard to children.…”

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confidence: 99%

Role of genotyping in Wilson’s disease

Schmidt

2009

Journal of Hepatology

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“…Most of the variants found in our study were reported before. Variant c.3472_3482del; p.Gly1158Phe*2 has been reported only in two other neighboring populations - Polish (Gromadzka et al 2005) and Lithuanians (Kucinskas et al 2008), suggesting that there could be a common ancestor in all three populations. Variant c.3620A>G (p.His1207Arg) has conflicting interpretation of pathogenicity in literature as it has been described as benign (Loudianos et al 1999) and pathogenic (Abdelghaffar et al 2008).…”

Section: Discussionmentioning

confidence: 97%

“…) and Lithuanians (Kucinskas et al. ), suggesting that there could be a common ancestor in all three populations. Variant c.3620A>G (p.His1207Arg) has conflicting interpretation of pathogenicity in literature as it has been described as benign (Loudianos et al.…”

Section: Discussionmentioning

confidence: 98%

Genetic variation spectrum in ATP7B gene identified in Latvian patients with Wilson disease

Zariņa

Tolmane

Kreile

et al. 2017

Molec Gen & Gen Med

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BackgroundWilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by allelic variants in ATP7B gene. More than 500 distinct variants have been reported, the most common WD causing allelic variant in the patients from Central, Eastern, and Northern Europe is H1069Q.MethodsAll Latvian patients with clinically confirmed WD were screened for the most common mutation p.H1069Q by PCR Bi‐PASA method. Direct DNA sequencing of gene ATP7B (all 21 exons) was performed for the patients with WD symptoms, being either heterozygous for H1069Q or without it on any allele.ResultsWe identified 15 different allelic variants along with eight non‐disease‐causing allelic variants. Based on the gene molecular analysis and patients' clinical data variant p.His1069Gln was found in 66.9% of WD alleles. Wide clinical variability was observed among individuals with the same ATP7B genotype. The results of our study confirm that neurological manifestations of WD are typically present later than the liver disease but no significant association between the presence/absence of the most common genetic variant and mode of initial WD presentation or age at presentation was identified.Conclusions(1) The most prevalent mutation in Latvian patients with Wilson disease was c.3207C>A (p.His1069Gln); (2) No significant phenotype–genotype correlation was found in Latvian patients with Wilson disease; (3) The estimated prevalence of Wilson disease in Latvia is 1 of 24,000 cases which is higher than frequently quoted prevalence of 1: 30,000.

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High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson’s disease

Abstract: The c.3207C>A (p.H1069Q) missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.

Cited by 18 publications

References 24 publications

Systems biology approach to Wilson’s disease

Systems biology approach to Wilson’s disease

Role of genotyping in Wilson’s disease

Genetic variation spectrum in ATP7B gene identified in Latvian patients with Wilson disease

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