title: Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies.
abstract: 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 alpha12 (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.
authors.affiliation: INSERM U 384, Faculté de Médecine, Place Henri Dunant, 63000 Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Vaurs-Barriere
authors.forename: M-N
authors.initials: MN
authors.lastname: Bonnet-Dupeyron
authors.forename: P
authors.initials: P
authors.lastname: Combes
authors.forename: F
authors.initials: F
authors.lastname: Gauthier-Barichard
authors.forename: X T
authors.initials: XT
authors.lastname: Reveles
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: D
authors.initials: D
authors.lastname: Rodriguez
authors.forename: P
authors.initials: P
authors.lastname: Vago
authors.forename: J A L
authors.initials: JA
authors.lastname: Armour
authors.forename: P
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
authors.forename: R J
authors.initials: RJ
authors.lastname: Leach
authors.forename: O
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D017931:DNA Primers; D015342:DNA Probes / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010264:Paraplegia / Q000235:genetics*; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D015342:DNA Probes; C499048:MBP protein, human; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C472930:PLP1 protein, human; D014157:Transcription Factors