X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease: Skewed in carriers of a duplication and random in carriers of point mutations

Karen Woodward, Karen Kirtland, Stephen Dlouhy, Wendy Raskind, Thomas Bird, Sue Malcolm, Dvorah Abeliovich

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalEuropean Journal of Human Genetics
Volume8
Issue number6
DOIs
StatePublished - Jun 2000

Fingerprint

Pelizaeus-Merzbacher Disease
X Chromosome Inactivation
Point Mutation
Phenotype
X Chromosome
Mutation
Chromosome Duplication
Gene Deletion
Genes

Keywords

  • Deletion
  • Duplication
  • Pelizaeus-Merzbacher disease
  • PLP
  • PMD
  • X inactivation

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease : Skewed in carriers of a duplication and random in carriers of point mutations. / Woodward, Karen; Kirtland, Karen; Dlouhy, Stephen; Raskind, Wendy; Bird, Thomas; Malcolm, Sue; Abeliovich, Dvorah.

In: European Journal of Human Genetics, Vol. 8, No. 6, 06.2000, p. 449-454.

Research output: Contribution to journalArticle

Woodward, Karen ; Kirtland, Karen ; Dlouhy, Stephen ; Raskind, Wendy ; Bird, Thomas ; Malcolm, Sue ; Abeliovich, Dvorah. / X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease : Skewed in carriers of a duplication and random in carriers of point mutations. In: European Journal of Human Genetics. 2000 ; Vol. 8, No. 6. pp. 449-454.
@article{312bc4f0671e44aa8aa0d464922fb33d,
title = "X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease: Skewed in carriers of a duplication and random in carriers of point mutations",
abstract = "Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD.",
keywords = "Deletion, Duplication, Pelizaeus-Merzbacher disease, PLP, PMD, X inactivation",
author = "Karen Woodward and Karen Kirtland and Stephen Dlouhy and Wendy Raskind and Thomas Bird and Sue Malcolm and Dvorah Abeliovich",
year = "2000",
month = "6",
doi = "10.1038/sj.ejhg.5200480",
language = "English",
volume = "8",
pages = "449--454",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease

T2 - Skewed in carriers of a duplication and random in carriers of point mutations

AU - Woodward, Karen

AU - Kirtland, Karen

AU - Dlouhy, Stephen

AU - Raskind, Wendy

AU - Bird, Thomas

AU - Malcolm, Sue

AU - Abeliovich, Dvorah

PY - 2000/6

Y1 - 2000/6

N2 - Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD.

AB - Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD.

KW - Deletion

KW - Duplication

KW - Pelizaeus-Merzbacher disease

KW - PLP

KW - PMD

KW - X inactivation

UR - http://www.scopus.com/inward/record.url?scp=0034119909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034119909&partnerID=8YFLogxK

U2 - 10.1038/sj.ejhg.5200480

DO - 10.1038/sj.ejhg.5200480

M3 - Article

C2 - 10878666

AN - SCOPUS:0034119909

VL - 8

SP - 449

EP - 454

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 6

ER -