Additional copies of the proteolipid protein gene causing Pelizaeus- Merzbacher disease arise by separate integration in to the X chromosome

M. E. Hodes, Karen Woodward, Nancy B. Spinner, Beverly S. Emanuel, Agnes Enrico-Simon, John Kamholz, Dwight Stambolian, Elaine H. Zackai, Victoria M. Pratt, I. T. Thomas, Kerry Crandall, Stephen Dlouhy, Sue Malcolm

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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.

Original languageEnglish
Pages (from-to)14-22
Number of pages9
JournalAmerican Journal of Human Genetics
Volume67
Issue number1
DOIs
StatePublished - 2000

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Pelizaeus-Merzbacher Disease
Proteolipids
X Chromosome
Proteins
Chromosomes
Inborn Genetic Diseases
Gene Duplication
Cytogenetic Analysis
Karyotype
Genes
Mutation

ASJC Scopus subject areas

  • Genetics

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Additional copies of the proteolipid protein gene causing Pelizaeus- Merzbacher disease arise by separate integration in to the X chromosome. / Hodes, M. E.; Woodward, Karen; Spinner, Nancy B.; Emanuel, Beverly S.; Enrico-Simon, Agnes; Kamholz, John; Stambolian, Dwight; Zackai, Elaine H.; Pratt, Victoria M.; Thomas, I. T.; Crandall, Kerry; Dlouhy, Stephen; Malcolm, Sue.

In: American Journal of Human Genetics, Vol. 67, No. 1, 2000, p. 14-22.

Research output: Contribution to journalArticle

Hodes, ME, Woodward, K, Spinner, NB, Emanuel, BS, Enrico-Simon, A, Kamholz, J, Stambolian, D, Zackai, EH, Pratt, VM, Thomas, IT, Crandall, K, Dlouhy, S & Malcolm, S 2000, 'Additional copies of the proteolipid protein gene causing Pelizaeus- Merzbacher disease arise by separate integration in to the X chromosome', American Journal of Human Genetics, vol. 67, no. 1, pp. 14-22. https://doi.org/10.1086/302965
Hodes, M. E. ; Woodward, Karen ; Spinner, Nancy B. ; Emanuel, Beverly S. ; Enrico-Simon, Agnes ; Kamholz, John ; Stambolian, Dwight ; Zackai, Elaine H. ; Pratt, Victoria M. ; Thomas, I. T. ; Crandall, Kerry ; Dlouhy, Stephen ; Malcolm, Sue. / Additional copies of the proteolipid protein gene causing Pelizaeus- Merzbacher disease arise by separate integration in to the X chromosome. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 1. pp. 14-22.
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