Periaxin mutations cause recessive Dejerine-Sottas neuropathy.
The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx(-/-) mice develop a severe demyelinating peripheral neuropathy, despite apparently normal initial formation of myelin sheaths. We hypothesized that mutations in PRX could cause human peripheral myelinopathies. In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation. We mapped PRX to 19q13.13-13.2, a region recently associated with a severe autosomal recessive demyelinating neuropathy in a Lebanese family (Delague et al. 2000) and syntenic to the location of Prx on murine chromosome 7 (Gillespie et al. 1997).
Boerkoel
C F
CF
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Takashima
H
H
Stankiewicz
P
P
Garcia
C A
CA
Leber
S M
SM
Rhee-Morris
L
L
Lupski
J R
JR
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002648:Child; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D005808:Genes, Recessive; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; C086745:periaxin; D004247:DNA