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Clinical presentation and mutations in Danish patients with Wilson disease

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@article{236d1ab9c79f400c84c808984873d777,
title = "Clinical presentation and mutations in Danish patients with Wilson disease",
abstract = "This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49 500. Among routinely used diagnostic tests, none were consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100{\%} of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70{\%} of mutations were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18{\%}. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25/27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations.",
keywords = "Adenosine Triphosphatases, Adolescent, Adult, Age of Onset, Cation Transport Proteins, Child, Female, Genetic Association Studies, Hepatolenticular Degeneration, Humans, Incidence, Male, Mutation Rate, Prevalence",
author = "M{\o}ller, {Lisbeth Birk} and Nina Horn and Jeppesen, {Tina Dysgaard} and John Vissing and Flemming Wibrand and Poul Jennum and Peter Ott",
year = "2011",
doi = "10.1038/ejhg.2011.80",
language = "English",
volume = "19",
pages = "935--41",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Clinical presentation and mutations in Danish patients with Wilson disease

AU - Møller, Lisbeth Birk

AU - Horn, Nina

AU - Jeppesen, Tina Dysgaard

AU - Vissing, John

AU - Wibrand, Flemming

AU - Jennum, Poul

AU - Ott, Peter

PY - 2011

Y1 - 2011

N2 - This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49 500. Among routinely used diagnostic tests, none were consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100% of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70% of mutations were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18%. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25/27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations.

AB - This study describes the clinical presentation and diagnosis in all Danish patients (49, 41 unrelated) with Wilson disease (WND). On the basis of the number of diagnosed patients from 1990-2008, the prevalence was estimated to be 1:49 500. Among routinely used diagnostic tests, none were consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100% of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70% of mutations were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18%. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25/27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations.

KW - Adenosine Triphosphatases

KW - Adolescent

KW - Adult

KW - Age of Onset

KW - Cation Transport Proteins

KW - Child

KW - Female

KW - Genetic Association Studies

KW - Hepatolenticular Degeneration

KW - Humans

KW - Incidence

KW - Male

KW - Mutation Rate

KW - Prevalence

U2 - 10.1038/ejhg.2011.80

DO - 10.1038/ejhg.2011.80

M3 - Journal article

VL - 19

SP - 935

EP - 941

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 9

ER -

ID: 33192974