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The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns
Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in FUCA...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827884/ https://www.ncbi.nlm.nih.gov/pubmed/33435586 http://dx.doi.org/10.3390/genes12010074 |
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author | Domin, Agnieszka Zabek, Tomasz Kwiatkowska, Aleksandra Szmatola, Tomasz Deregowska, Anna Lewinska, Anna Mazur, Artur Wnuk, Maciej |
author_facet | Domin, Agnieszka Zabek, Tomasz Kwiatkowska, Aleksandra Szmatola, Tomasz Deregowska, Anna Lewinska, Anna Mazur, Artur Wnuk, Maciej |
author_sort | Domin, Agnieszka |
collection | PubMed |
description | Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in FUCA1 encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. FUCA1 mutations lead to severe reduction or even loss of α-L-fucosidase enzyme activity. This results in incomplete breakdown of fucose-containing compounds leading to their deposition in different tissues and, consequently, disease progression. To date, 36 pathogenic variants in FUCA1 associated with fucosidosis have been documented. Among these are three splice site variants. Here, we report a novel fucosidosis-related 9-base-pair deletion (NG_013346.1:g.10233_10241delACAGGTAAG) affecting the exon 3/intron 3 junction within a FUCA1 sequence. This novel pathogenic variant was identified in a five-year-old Polish girl with a well-defined pattern of fucosidosis symptoms. Since it is postulated that other genetic, nongenetic or environmental factors can also contribute to fucosidosis pathogenesis, we performed further analysis and found two rare de novo chromosomal aberrations in the girl’s genome involving a 15q11.1-11.2 microdeletion and an Xq22.2 gain. These abnormalities were associated with genome-wide changes in DNA methylation status in the epigenome of blood cells. |
format | Online Article Text |
id | pubmed-7827884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78278842021-01-25 The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns Domin, Agnieszka Zabek, Tomasz Kwiatkowska, Aleksandra Szmatola, Tomasz Deregowska, Anna Lewinska, Anna Mazur, Artur Wnuk, Maciej Genes (Basel) Article Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in FUCA1 encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. FUCA1 mutations lead to severe reduction or even loss of α-L-fucosidase enzyme activity. This results in incomplete breakdown of fucose-containing compounds leading to their deposition in different tissues and, consequently, disease progression. To date, 36 pathogenic variants in FUCA1 associated with fucosidosis have been documented. Among these are three splice site variants. Here, we report a novel fucosidosis-related 9-base-pair deletion (NG_013346.1:g.10233_10241delACAGGTAAG) affecting the exon 3/intron 3 junction within a FUCA1 sequence. This novel pathogenic variant was identified in a five-year-old Polish girl with a well-defined pattern of fucosidosis symptoms. Since it is postulated that other genetic, nongenetic or environmental factors can also contribute to fucosidosis pathogenesis, we performed further analysis and found two rare de novo chromosomal aberrations in the girl’s genome involving a 15q11.1-11.2 microdeletion and an Xq22.2 gain. These abnormalities were associated with genome-wide changes in DNA methylation status in the epigenome of blood cells. MDPI 2021-01-08 /pmc/articles/PMC7827884/ /pubmed/33435586 http://dx.doi.org/10.3390/genes12010074 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Domin, Agnieszka Zabek, Tomasz Kwiatkowska, Aleksandra Szmatola, Tomasz Deregowska, Anna Lewinska, Anna Mazur, Artur Wnuk, Maciej The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title | The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title_full | The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title_fullStr | The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title_full_unstemmed | The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title_short | The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns |
title_sort | identification of a novel fucosidosis-associated fuca1 mutation: a case of a 5-year-old polish girl with two additional rare chromosomal aberrations and affected dna methylation patterns |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827884/ https://www.ncbi.nlm.nih.gov/pubmed/33435586 http://dx.doi.org/10.3390/genes12010074 |
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