PLA2G6 mutation underlies infantile neuroaxonal dystrophy.
Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive neurodegenerative disease that presents within the first 2 years of life and culminates in death by age 10 years. Affected individuals from two unrelated Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse cerebellar atrophy and abnormal iron deposition in the medial and lateral globus pallidum. Progressive white-matter disease and reduction of the N-acetyl aspartate : chromium ratio were evident on magnetic resonance spectroscopy, suggesting loss of myelination. The clinical and radiological diagnosis of INAD was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP rs139897), and an underlying mutation common to both affected families was identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic, calcium-independent). These findings highlight a role of phospholipase in neurodegenerative disorders.
Khateeb
Shareef
S
Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben-Gurion University, Israel.
Flusser
Hagit
H
Ofir
Rivka
R
Shelef
Ilan
I
Narkis
Ginat
G
Vardi
Gideon
G
Shorer
Zamir
Z
Levy
Rachel
R
Galil
Aharon
A
Elbedour
Khalil
K
Birk
Ohad S
OS
D000595:Amino Acid Sequence; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007557:Israel; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D010741:Phospholipases A; D054467:Phospholipases A2