PLA2G6 Mutation Underlies Infantile Neuroaxonal Dystrophy

• Published in: American journal of human genetics 2006-11, Vol.79 (5), p.942-948
• Main Authors: Khateeb, Shareef, Flusser, Hagit, Ofir, Rivka, Shelef, Ilan, Narkis, Ginat, Vardi, Gideon, Shorer, Zamir, Levy, Rachel, Galil, Aharon, Elbedour, Khalil, Birk, Ohad S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Brain - pathology; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 22 - genetics; Consanguinity; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genes, Recessive; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Humans; Infant; Israel; Lod Score; Magnetic Resonance Imaging; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Muscular dystrophy; Mutation; Neuroaxonal Dystrophies - enzymology; Neuroaxonal Dystrophies - genetics; Neuroaxonal Dystrophies - pathology; Neurological disorders; Neurology; Pedigree; Phenotype; Phospholipases A - genetics; Phospholipases A2; Sequence Deletion; Sequence Homology, Amino Acid
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/508572

Infantile neuro axonal 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.