A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome

Milena Cau, Maria Addis, Rita Congiu, Cristiana Meloni, Antonio Cao, Simona Santaniello, Mario Loi, Francesco Emma, Orsetta Zuffardi, Roberto Ciccone, Gabriella Sole, Maria Antonietta Melis

Research output: Contribution to journalArticle

Abstract

In mammals, X-linked gene products can be dosage compensated between males and females by inactivation of one of the two X chromosomes in the developing female embryos. X inactivation choice is usually random in embryo mammals, but several mechanisms can influence the choice determining skewed X inactivation. As a consequence, females heterozygous for X-linked recessive disease can manifest the full phenotype. Herein, we report a family with extremely skewed X inactivation that produced the full phenotype of Lowe syndrome, a recessive X-linked disease, in a female. The X chromosome inactivation studies detected an extremely skewed inactivation pattern with a ratio of 100:0 in the propositus as well as in five out of seven unaffected female relatives in four generations. The OCRL1 "de novo" mutation resides in the active paternally inherited X chromosome. X chromosome haplotype analysis suggests the presence of a locus for the familial skewed X inactivation in chromosome Xq25 most likely controlling X chromosome choice in X inactivation or cell proliferation. The description of this case adds Lowe syndrome to the list of X-linked disorders which may manifest the full phenotype in females because of the skewed X inactivation.

Original languageEnglish
Pages (from-to)1030-1036
Number of pages7
JournalJournal of Human Genetics
Volume51
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • Family study
  • Lowe syndrome
  • Skewed X inactivation
  • X chromosome inactivation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Cau, M., Addis, M., Congiu, R., Meloni, C., Cao, A., Santaniello, S., Loi, M., Emma, F., Zuffardi, O., Ciccone, R., Sole, G., & Melis, M. A. (2006). A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome. Journal of Human Genetics, 51(11), 1030-1036. https://doi.org/10.1007/s10038-006-0049-6