Journal article
Additional Copies of the Proteolipid Protein Gene Causing Pelizaeus-Merzbacher Disease Arise by Separate Integration into the X Chromosome
American journal of human genetics, Vol.67(1), pp.14-22
2000
DOI: 10.1086/302965
PMCID: PMC1287072
PMID: 10827108
Abstract
The proteolipid protein gene (
PLP) is normally present at chromosome Xq22. Mutations and duplications of this gene are associated with Pelizaeus-Merzbacher disease (PMD). Here we describe two new families in which males affected with PMD were found to have a copy of
PLP on the short arm of the X chromosome, in addition to a normal copy on Xq22. In the first family, the extra copy was first detected by the presence of heterozygosity of the
AhaII dimorphism within the
PLP gene. The results of FISH analysis showed an additional copy of
PLP in Xp22.1, although no chromosomal rearrangements could be detected by standard karyotype analysis. Another three affected males from the family had similar findings. In a second unrelated family with signs of PMD, cytogenetic analysis showed a pericentric inversion of the X chromosome. In the inv(X) carried by several affected family members, FISH showed
PLP signals at Xp11.4 and Xq22. A third family has previously been reported, in which affected members had an extra copy of the
PLP gene detected at Xq26 in a chromosome with an otherwise normal banding pattern. The identification of three separate families in which
PLP is duplicated at a noncontiguous site suggests that such duplications could be a relatively common but previously undetected cause of genetic disorders.
Details
- Title: Subtitle
- Additional Copies of the Proteolipid Protein Gene Causing Pelizaeus-Merzbacher Disease Arise by Separate Integration into the X Chromosome
- Creators
- M.E Hodes - Department of Medical and Molecular Genetics, Indiana University School of Medicine, IndianapolisKaren Woodward - Clinical and Molecular Genetics Unit, Institute of Child Health, LondonNancy B Spinner - Division of Human Genetics and Molecular Biology, The Children’s Hospital of PhiladelphiaBeverly S Emanuel - Division of Human Genetics and Molecular Biology, The Children’s Hospital of PhiladelphiaAgnes Enrico-Simon - Division of Human Genetics and Molecular Biology, The Children’s Hospital of PhiladelphiaJohn Kamholz - Division of Human Genetics and Molecular Biology, The Children’s Hospital of PhiladelphiaDwight Stambolian - Department of Ophthalmology, University of Pennsylvania School of Medicine, PhiladelphiaElaine H Zackai - Division of Human Genetics and Molecular Biology, The Children’s Hospital of PhiladelphiaVictoria M Pratt - Department of Medical and Molecular Genetics, Indiana University School of Medicine, IndianapolisI.T Thomas - Bowman Gray School of Medicine, Winston-Salem, North CarolinaKerry Crandall - Division of Maternal and Child Health, North Carolina Department of Environment, Health and Natural Resources, Black Mountain, NCStephen R Dlouhy - Department of Medical and Molecular Genetics, Indiana University School of Medicine, IndianapolisSue Malcolm - Clinical and Molecular Genetics Unit, Institute of Child Health, London
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.67(1), pp.14-22
- Publisher
- Elsevier Inc
- DOI
- 10.1086/302965
- PMID
- 10827108
- PMCID
- PMC1287072
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 2000
- Academic Unit
- Neurology; Psychiatry
- Record Identifier
- 9984020783002771
Metrics
33 Record Views