PLP1 gene analysis in 88 patients with leukodystrophy.
Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.
INGEMM, IdIPAZ, CIBERER, Hospital Universitario La Paz, Madrid, Spain.
P
P
Martínez-Montero
M
M
Muñoz-Calero
E
E
Vallespín
J
J
Campistol
L
L
Martorell
M J
MJ
Ruiz-Falcó
A
A
Santana
R
R
Pons
A
A
Dinopoulos
C
C
Sierra
J
J
Nevado
J
J
Molano
D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype
D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
PLP1 mutations; Pelizaeus-Merzbacher disease; array- CGH; leukodystrophy