Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F17%3A10378814" target="_blank" >RIV/00064165:_____/17:10378814 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/17:10378814

Result on the web

<a href="https://fb.cuni.cz/file/5852/fb2017a0023.pdf" target="_blank" >https://fb.cuni.cz/file/5852/fb2017a0023.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease

Original language description

Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C&gt;T (p.Gln724Ter); c.3745G&gt;T (p.Glu1249Ter); and c.3862C&gt;T (p.Gln1288Ter). The mutation c.3745G&gt;T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/GB14-36804G" target="_blank" >GB14-36804G: Centre of mitochondrial biology and pathology (MITOCENTRE)</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Folia Biologica

ISSN

0015-5500

e-ISSN

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Volume of the periodical

63

Issue of the periodical within the volume

5-6

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

9

Pages from-to

165-173

UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-85046118037