Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis
L Basel‐Vanagaite, L Muncher… - Annals of Neurology …, 2006 - Wiley Online Library
L Basel‐Vanagaite, L Muncher, R Straussberg, M Pasmanik‐Chor, M Yahav, L Rainshtein…
Annals of Neurology: Official Journal of the American Neurological …, 2006•Wiley Online LibraryObjective 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 230kb 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 …
infantile bilateral striatal necrosis. Methods We have mapped the disease gene in the
candidate region to approximately 230kb 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 …
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 230kb 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. Ann Neurol 2006
Wiley Online Library