GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease.
BACKGROUND
Pelizaeus-Merzbacher-like disease (PMLD) is a genetically heterogeneous disorder within the group of hypomyelinating leukoencephalopathies. Mutations of the gap junction protein alpha 12 (GJA12) gene are known to cause one autosomal recessive PMLD form. Few patients with GJA12 mutated PMLD have been reported, and to date, the frequency as well as the genotypic and phenotypic spectrum of GJA12 related PMLD is unclear.


METHODS
We report mutation analysis of the GJA12 gene in a clinical and radiologic well-characterized multiethnic cohort of 193 patients with PMLD from 182 families.


CONCLUSIONS
Only 16 patients (8.3%) from 14 families (7.7%) carry GJA12 mutations including five families where we detected only one mutated allele. Among those, we identified 11 novel alterations. Thus, GJA12 mutations are a rather rare cause for Pelizaeus-Merzbacher-like disease. The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1 (PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.
Henneke
M
M
Department of Pediatrics and Pediatric Neurology, Georg August University, Faculty of Medicine, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Combes
P
P
Diekmann
S
S
Bertini
E
E
Brockmann
K
K
Burlina
A P
AP
Kaiser
J
J
Ohlenbusch
A
A
Plecko
B
B
Rodriguez
D
D
Boespflug-Tanguy
O
O
Gärtner
J
J
D000293:Adolescent; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017629:Gap Junctions / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D017630:Connexins; D005819:Genetic Markers; D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human; C427305:connexin 47