Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis

Objective: The objective of this study was to identify the gene causing autosomal recessive infantile bilateral striatal necrosis. Methods: We have mapped the disease gene in the candidate region to approximately 230k6 on 19q13.33 in 8 interrelated families including a total of 12 patients and 39 unaffected individuals. Results: Sequencing of the nup62 gene showed a missense mutation causing a change from glutamine to proline (Q391P) in all the patients, producing a substitution from a polar, hydrophilic residue to a nonpolar, neutral residue. All the other 12 candidate genes were sequenced, and no pathogenic sequence changes were found. Comparisons of p62 protein sequences from diverse species indicate that glutamine at position 391 is highly conserved. Five prenatal diagnoses were performed in three at-risk families. Interpretation: This is the second example of a nuclear pore complex protein causing mendelian disease in humans (the first one is triple A syndrome). Our findings suggest that p62 has a cell type-specific role and is important in the degeneration of the basal ganglia in humans.