Clinical presentation and mutations in Danish patients with Wilson disease

Lisbeth Birk Møller; Nina Horn; Tina Dysgaard Jeppesen; John Vissing; Flemming Wibrand; Poul Jennum; Peter Ott

doi:http://dx.doi.org/10.1038/ejhg.2011.80

Clinical presentation and mutations in Danish patients with Wilson disease

Lisbeth Birk Møller, Nina Horn, Tina Dysgaard Jeppesen, John Vissing, Flemming Wibrand, Poul Jennum, Peter Ott

28 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Human Genetics
Vol/bind	19
Udgave nummer	9
Sider (fra-til)	935-41
Antal sider	7
ISSN	1018-4813
DOI	https://doi.org/10.1038/ejhg.2011.80
Status	Udgivet - sep. 2011

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http://dx.doi.org/10.1038/ejhg.2011.80

Citationsformater

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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.",

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",

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doi = "http://dx.doi.org/10.1038/ejhg.2011.80",

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pages = "935--41",

journal = "European Journal of Human Genetics",

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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 - 2011/9

Y1 - 2011/9

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.

U2 - http://dx.doi.org/10.1038/ejhg.2011.80

DO - http://dx.doi.org/10.1038/ejhg.2011.80

M3 - Journal article

SN - 1018-4813

VL - 19

SP - 935

EP - 941

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 9

ER -

Clinical presentation and mutations in Danish patients with Wilson disease

Abstract

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