title: Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis.
abstract: A family with an apparent history of X-linked Pelizaeus-Merzbacher disease presented for genetic counseling, requesting carrier detection and prenatal diagnosis. RFLP analysis using the proteolipid protein (PLP) gene probe was uninformative in this family. A prenatal diagnosis on a chorionic villus sample (CVS) was carried out using single-strand conformation polymorphism (SSCP) analysis of a variant in exon 4 of the PLP gene. The fetus was predicted to be unaffected. Sequencing of the exon from the CVS, the predicted-carrier mother, and the obligate-carrier grandmother revealed an A-to-C change at nucleotide 541 in the two women but not in the fetus. As this change results in a Thr-to-Pro change at amino acid 181 in a region of the gene predicted to be part of a transmembrane segment, it was concluded that this was the mutation causing the disease in this family. In addition, in a second family, an exon 5 variant band pattern on SSCP analysis was shown by sequencing to be due to a T-to-C change at nucleotide 668. This results in a Leu-to-Pro change in a carrier mother and in her two affected sons. These results provide further examples of mutations in PLP that cause Pelizaeus-Merzbacher disease and illustrate the value of SSCP in genetic analysis.
authors.affiliation: Molecular Genetics Unit, Institute of Child Health, London, England.
authors.forename: S
authors.initials: S
authors.lastname: Strautnieks
authors.forename: P
authors.initials: P
authors.lastname: Rutland
authors.forename: R M
authors.initials: RM
authors.lastname: Winter
authors.forename: M
authors.initials: M
authors.lastname: Baraitser
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015193:Chorionic Villi Sampling; D004247:DNA / Q000235:genetics; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D007231:Infant, Newborn; D007930:Leucine; D008297:Male; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011392:Proline; D015183:Restriction Mapping; D013912:Threonine; D014960:X Chromosome
chemical_list: D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D009838:Oligodeoxyribonucleotides; D013912:Threonine; D004247:DNA; D011392:Proline; D007930:Leucine