Pelizaeus-Merzbacher disease: Detection of mutations Thr[sup 181][yields]Pro and Leu[sup 223][yields]Pro in the proteolipid protein gene, and prenatal diagnosis
- Institute of Child Health, London (United Kingdom)
- Northwick Park Hospital, Middlesex (United Kingdom)
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 (SSC) 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. 17 refs., 6 figs., 1 tab.
- OSTI ID:
- 5032017
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 51:4; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GENE MUTATIONS
DETECTION
MEMBRANE PROTEINS
NERVOUS SYSTEM DISEASES
DNA SEQUENCING
GENETIC MAPPING
HUMAN X CHROMOSOME
CHROMOSOMES
DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
MAPPING
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
X CHROMOSOME
550400* - Genetics