TY - JOUR
T1 - Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies
AU - Vaurs-Barriere, C.
AU - Bonnet-Dupeyron, M. N.
AU - Combes, P.
AU - Gauthier-Barichard, F.
AU - Reveles, X. T.
AU - Schiffmann, R.
AU - Bertini, E.
AU - Rodriguez, D.
AU - Vago, P.
AU - Armour, J. A.L.
AU - Saugier-Veber, P.
AU - Frebourg, T.
AU - Leach, R. J.
AU - Boespflug-Tanguy, Odile
PY - 2006/1
Y1 - 2006/1
N2 - The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein α12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation.
AB - The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein α12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation.
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U2 - 10.1111/j.1529-8817.2005.00208.x
DO - 10.1111/j.1529-8817.2005.00208.x
M3 - Article
C2 - 16441258
AN - SCOPUS:33644829799
SN - 0003-4800
VL - 70
SP - 66
EP - 77
JO - Annals of Human Genetics
JF - Annals of Human Genetics
IS - 1
ER -