AUTHOR=Kou Mengyao , Ren Bin , Xing Mengnan , Chen Lijuan , Xu Xiangping 

TITLE=Retropseudogene insertion generated through retrotransposition in the ATP7A gene results in premature stop codons and a case of Menkes disease

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1680208

DOI=10.3389/fneur.2025.1680208

ISSN=1664-2295

ABSTRACT=Pathogenic variants in the ATP7A gene, which encodes a transmembrane copper-transporting P-type ATPase, underlie Menkes disease, a rare X-linked recessive disorder of copper metabolism. We report a 3-year-old boy presenting with progressive neurodegeneration, refractory epilepsy, connective tissue abnormalities, and characteristic kinky hair. Whole-exome sequencing and confirmatory analysis identified a retropseudogene insertion (~500 bp) in exon 3 of ATP7A, displaying the hallmarks of target-primed reverse transcription. PCR and RNA-seq revealed a marked reduction in ATP7A transcript levels in the patient. This case underscores the diagnostic relevance of retropseudogene insertions in disease genes and highlights their role in human pathology.