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

• Published in: Genes 2021-01, Vol.12 (1), p.74
• Main Authors: Domin, Agnieszka, Zabek, Tomasz, Kwiatkowska, Aleksandra, Szmatola, Tomasz, Deregowska, Anna, Lewinska, Anna, Mazur, Artur, Wnuk, Maciej
• Format: Article
• Language: English
• Subjects: Annealing; Blood cells; Chromosome aberrations; Chromosomes; Deoxyribonucleic acid; DNA; DNA methylation; Environmental factors; Enzymatic activity; Enzymes; Epigenetics; Fucose; Fucosidosis; Gene deletion; Genomes; Glycolipids; Glycoproteins; Growth rate; Hereditary diseases; Intellectual disabilities; Mutation; Pathogenesis; Software
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12010074

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 encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. 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 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 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.