Giant axonal neuropathy caused by compound heterozygosity for a maternally inherited microdeletion and a paternal mutation within the GAN gene.
Different missense, nonsense and frameshift mutations in the GAN gene encoding gigaxonin have been described to cause giant axonal neuropathy, a severe early-onset progressive neurological disease with autosomal recessive inheritance. By oligonucleotide array CGH analysis, we identified a 57-131 kb microdeletion affecting this gene in a patient with developmental delay, ataxia, areflexia, macrocephaly, and strikingly frizzy hair. The microdeletion was inherited from the mother and mutation analysis revealed a paternally inherited missense mutation c.1456G>A in exon 9 on the other allele. Our findings illustrate the power of higher resolution array CGH studies and highlight the importance of considering copy number variations in autosomal recessive diseases.
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Karen
K
Buysse
Sarah
S
Vergult
Silke
S
Mussche
Chantal
C
Ceuterick-de Groote
Frank
F
Speleman
Björn
B
Menten
Willy
W
Lissens
Rudy
R
Van Coster
D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D056768:Giant Axonal Neuropathy / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
D003598:Cytoskeletal Proteins; C416508:GAN protein, human