Novel Non-coding Variant in GALT

Introduction
Classic galactosemia is a genetically recessive disease caused by mutations in GALT gene, meaning a child has to inherit one defective gene from each parent before having galactosemia.

Galactosemia poses as a lethal threat to the lives of newborn babies, hence newborn screening (NBS) is usually carried out after the birth of a child to detect classic galactosemia.  However, this molecular diagnosis can become quite complicated due to the extensive and overlapping range of reactions involving GALT enzyme.
Allelic heterogeneity at the GALT locus - the gene location which encodes for GALT - also contributes to these complications. Allelic heterogeneity is a phenomenon whereby different mutations at the same locus causes the same phenotype. Meaning to say that, in some cases, the mutated GALT gene can still encode for GALT enzyme despite the belief that a mutated GALT gene cannot encode for  the GALT enzyme. Hence, due to these complications, NBS can sometimes generate false positive results for galactosemia during screenings.

Discovering the Non-coding Variant
A scientific finding was recently published in ScienceDirect revealing a novel non-coding variant, c.377+17C>T, in the GALT gene. This non-coding variant in the GALT gene is believed to be associated with false positive newborn screening results for galactosemia.

After conducting qRT-PCR studies on the lymphoblasts of the child flagged for galactosemia, the scientists found that his GALT-mRNA levels were normal. The values of Gal-1P, an intermediate in the intraconversion of glucose and galactose, in the child were also measured to be normal after exposure to galactose.
The novel non-coding GALT variant, c.377+17C>T, was later found to be homozygous in the child and heterozygous in the parents.

Conclusion
The existence of these rare but benign variants in the GALT gene highlights the need for further functional studies to distinguish benign variants from malign variants so as to prevent future false positive newborn screening results.