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 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.


CONCLUSIONS
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.
Basel-Vanagaite
Lina
L
Department of Medical Genetics, Schneider Children's Medical Center of Israel and Rabin Medical Center, Petah Tikva, Israel. basel@post.tau.ac.il
Muncher
Liora
L
Straussberg
Rachel
R
Pasmanik-Chor
Metsada
M
Yahav
Michal
M
Rainshtein
Limor
L
Walsh
Christopher A
CA
Magal
Nurit
N
Taub
Ellen
E
Drasinover
Valerie
V
Shalev
Hanna
H
Attia
Revital
R
Rechavi
Gideon
G
Simon
Amos J
AJ
Shohat
Mordechai
M
D000328:Adult; D018912:Arabs; D015153:Blotting, Western; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009154:Mutation / Q000502:physiology*; D009336:Necrosis; D017072:Neostriatum / Q000473:pathology*; D028861:Nuclear Pore Complex Proteins; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; C049312:nuclear pore protein p62; D004247:DNA