A silent nucleotide substitution in the ATP7A gene in a child with Menkes disease

We present a case of classical Menkes disease (MD) due to a novel “silent” substitution in the ATP7A gene; c.2781G>A (p.K927K). The affected nucleotide is the last nucleotide in exon 13, and affects mRNA splicing. Transcripts missing exon 13; and transcripts missing exons 11, 12 and 13 in addition to a very small amount of normal spliced ATP7A transcripts were expressed. This is the first report of a synonymous ATP7A substitution being responsible for MD. •Apparently silent substitutions can be pathogenic.•Silent substitutions might affect splicing.•Female carriers of Menkes Disease might have a higher risk of congenital hearth disease.•The presence of only 0.85%, of the amount found in healthy control sample, full-length transcript most likely explains the severe phenotype.