Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis.
Am J Hum Genet
; 51(4): 871-8, 1992 Oct.
Article
in En
| MEDLINE
| ID: mdl-1384324
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prenatal Diagnosis
/
X Chromosome
/
Polymorphism, Restriction Fragment Length
/
Diffuse Cerebral Sclerosis of Schilder
/
Myelin Proteins
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Newborn
/
Pregnancy
Language:
En
Journal:
Am J Hum Genet
Year:
1992
Document type:
Article
Affiliation country:
United kingdom