Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Domin, Agnieszka, Zabek, Tomasz, Kwiatkowska, Aleksandra, Szmatola, Tomasz, Deregowska, Anna, Lewinska, Anna, Mazur, Artur, Wnuk, Maciej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783640876042420224
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
work_keys_str_mv AT dominagnieszka theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT zabektomasz theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT kwiatkowskaaleksandra theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT szmatolatomasz theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT deregowskaanna theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT lewinskaanna theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT mazurartur theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT wnukmaciej theidentificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT dominagnieszka identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT zabektomasz identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT kwiatkowskaaleksandra identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT szmatolatomasz identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT deregowskaanna identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT lewinskaanna identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT mazurartur identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns
AT wnukmaciej identificationofanovelfucosidosisassociatedfuca1mutationacaseofa5yearoldpolishgirlwithtwoadditionalrarechromosomalaberrationsandaffecteddnamethylationpatterns