Linkage of Pelizaeus-Merzbacher disease in a large family to the PLP region
- Indiana Univ. School of Medicine, Indianapolis, IN (United States); and others
Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder of the CNS. Three-fourths of patients have no defects in the coding region of the proteolipid protein gene (PLP). To determine whether PMD in such patients is linked to PLP, we examined a large 4-generational PMD family with 16 typed members. This family has no mutations in the coding region or in 1 kb 5{prime} of the first exon and 150 bp following the terminal polyadenylation site. A series of microsatellite markers spanning 20-30 cM around PLP was examined to determine whether the gene in this family was linked to this region. No recombinants were observed with three markers: DXS178 (Zmax=2.76), MFD72 (Zmax=1.20) and DXS3 (Zmax=1.20). Two point LOD scores with the other markers in this region supported a putative disease gene in this region. Multipoint analysis was performed and the proximal and distal portions of this region could be eliminated as possible sites of the disease gene. The other intervals between markers in this region could not be eliminated statistically. PLP has been localized by physical mapping between DXS178 and COL4A5. The disease gene in this family also appears to be in this larger PLP region, although because of the size of the family we can not eliminate statistically the intervals between the markers around, but not adjacent to, the PLP gene. The mapping of this PMD family without a recognizable mutation to the PLP region is significant since it supports the hypothesis that the disease-causing genetic defect in this and similar families is located at or near PLP.
- OSTI ID:
- 134101
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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