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.
Buysse
Karen
K
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Vergult
Sarah
S
Mussche
Silke
S
Ceuterick-de Groote
Chantal
C
Speleman
Frank
F
Menten
Björn
B
Lissens
Willy
W
Van Coster
Rudy
R
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