First Report of Missense Mutation at c.1664A>G (p.Y555C) in Krabbe Disease: Genomic Analysis in the Diagnosis of Genetic Disorders

OBJECTIVES: Genetic disorders contribute to severe morbidity and mortality among neonates and children. Most of these conditions could be attributed to the inheritance of defective gene/chromosome from the parents. Consanguinity, or coming from the same ancestral lineage is considered as a predisposing factor for the development of genetic anomalies. Krabbe disease or globoid cell leukodystrophy is an autosomal recessive disorder due to the mutation of the gene coding for galactosyl ceramidase or galactocerebrosidase (GALC gene). We present a brief report of Krabbe disease attributed to a missense mutation at C.1664A>G (p.Y555C) in exon 14, which was previously not reported in the literature as a pathogenic variant. METHODS: A combination of clinical symptoms and laboratory diagnostic methods were used to diagnose the Krabbe disease/globoid cell leukodystrophy. The deoxyribonucleic acid (DNA) sequencing for GALC gene and flanking intronic regions and an enzyme analysis was done to confirm Krabbe disease. Mutational analysis of GALC gene and flanking intronic regions was performed (Sequence analysis of 12 exons (exons-2, 3, 4, 6, 8, 9, 11, 12, 13, 14, 15, 16 & 18). RESULTS: A homozygous silent mutation at c.1350C>T (p.5450S) in exon 13, a homozygous missense mutation at c.1664C >G (p.Y555C) in exon 14, homozygous silent mutation at c. 1685T>C (p. I562I) in exon 15, homozygous silent mutation at c. 1698A>T (p. V566V) in exon 15, and a homozygous intronic variant IVS15+5C>G was observed. CONCLUSION: A homozygous missense mutation at c.1664C >G (p.Y555C) in exon 14 was observed along with undetectable enzyme activities of β-galactocerebrosidase for the first time in a patient with Krabbe disease.