Case Report: A retrotransposon insertion in the ATP7A gene results in premature stop codons and causes Menkes diseas

Pathogenic variants in the ATP7A gene, which encodes a transmembrane copper transporter P-type ATPase, cause a rare X-linked recessive disorder of copper metabolism, known as Menkes disease. Here we describe a 3-year-old boy with progressive neurodegeneration, intractable epilepsy, connective tissue disturbances, and peculiar kinky hair. A retrotransposon insertion (~500 bp) in exon 3 of the ATP7A gene was discovered by WES and sequence analysis. The insertion bears hallmarks of target-primed reverse transcription. Using PCR and RNA-seq, we documented the dramatic decrease in ATP7A transcript production in the patient. This observation highlights the importance of identifying retrotransposon disease genes for diagnosis.