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Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly
Microcephaly is a devastating condition defined by a small head and small brain compared to the age- and sex-matched population. Mutations in a number of different genes causative for microcephaly have been identified, e.g., MCPH1, WDR62, and ASPM. Recently, mutations in the gene encoding the enzyme...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053511/ https://www.ncbi.nlm.nih.gov/pubmed/30057589 http://dx.doi.org/10.3389/fgene.2018.00245 |
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author | Schleinitz, Dorit Seidel, Anna Stassart, Ruth Klammt, Jürgen Hirrlinger, Petra G. Winkler, Ulrike Köhler, Susanne Heiker, John T. Schönauer, Ria Bialek, Joanna Krohn, Knut Hoffmann, Katrin Kovacs, Peter Hirrlinger, Johannes |
author_facet | Schleinitz, Dorit Seidel, Anna Stassart, Ruth Klammt, Jürgen Hirrlinger, Petra G. Winkler, Ulrike Köhler, Susanne Heiker, John T. Schönauer, Ria Bialek, Joanna Krohn, Knut Hoffmann, Katrin Kovacs, Peter Hirrlinger, Johannes |
author_sort | Schleinitz, Dorit |
collection | PubMed |
description | Microcephaly is a devastating condition defined by a small head and small brain compared to the age- and sex-matched population. Mutations in a number of different genes causative for microcephaly have been identified, e.g., MCPH1, WDR62, and ASPM. Recently, mutations in the gene encoding the enzyme asparagine synthetase (ASNS) were associated to microcephaly and so far 24 different mutations in ASNS causing microcephaly have been described. In a family with two affected girls, we identified novel compound heterozygous variants in ASNS (c.1165G > C, p.E389Q and c.601delA, p.M201Wfs(∗)28). The first mutation (E389Q) is a missense mutation resulting in the replacement of a glutamate residue evolutionary conserved from Escherichia coli to Homo sapiens by glutamine. Protein modeling based on the known crystal structure of ASNS of E. coli predicted a destabilization of the protein by E389Q. The second mutation (p.M201Wfs(∗)28) results in a premature stop codon after amino acid 227, thereby truncating more than half of the protein. The novel variants expand the growing list of microcephaly causing mutations in ASNS. |
format | Online Article Text |
id | pubmed-6053511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60535112018-07-27 Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly Schleinitz, Dorit Seidel, Anna Stassart, Ruth Klammt, Jürgen Hirrlinger, Petra G. Winkler, Ulrike Köhler, Susanne Heiker, John T. Schönauer, Ria Bialek, Joanna Krohn, Knut Hoffmann, Katrin Kovacs, Peter Hirrlinger, Johannes Front Genet Genetics Microcephaly is a devastating condition defined by a small head and small brain compared to the age- and sex-matched population. Mutations in a number of different genes causative for microcephaly have been identified, e.g., MCPH1, WDR62, and ASPM. Recently, mutations in the gene encoding the enzyme asparagine synthetase (ASNS) were associated to microcephaly and so far 24 different mutations in ASNS causing microcephaly have been described. In a family with two affected girls, we identified novel compound heterozygous variants in ASNS (c.1165G > C, p.E389Q and c.601delA, p.M201Wfs(∗)28). The first mutation (E389Q) is a missense mutation resulting in the replacement of a glutamate residue evolutionary conserved from Escherichia coli to Homo sapiens by glutamine. Protein modeling based on the known crystal structure of ASNS of E. coli predicted a destabilization of the protein by E389Q. The second mutation (p.M201Wfs(∗)28) results in a premature stop codon after amino acid 227, thereby truncating more than half of the protein. The novel variants expand the growing list of microcephaly causing mutations in ASNS. Frontiers Media S.A. 2018-07-13 /pmc/articles/PMC6053511/ /pubmed/30057589 http://dx.doi.org/10.3389/fgene.2018.00245 Text en Copyright © 2018 Schleinitz, Seidel, Stassart, Klammt, Hirrlinger, Winkler, Köhler, Heiker, Schönauer, Bialek, Krohn, Hoffmann, Kovacs and Hirrlinger. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Schleinitz, Dorit Seidel, Anna Stassart, Ruth Klammt, Jürgen Hirrlinger, Petra G. Winkler, Ulrike Köhler, Susanne Heiker, John T. Schönauer, Ria Bialek, Joanna Krohn, Knut Hoffmann, Katrin Kovacs, Peter Hirrlinger, Johannes Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title | Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title_full | Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title_fullStr | Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title_full_unstemmed | Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title_short | Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly |
title_sort | novel mutations in the asparagine synthetase gene (asns) associated with microcephaly |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053511/ https://www.ncbi.nlm.nih.gov/pubmed/30057589 http://dx.doi.org/10.3389/fgene.2018.00245 |
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