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

J Hum Genet. 2006;51(11):1030-1036. doi: 10.1007/s10038-006-0049-6. Epub 2006 Sep 6.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X*
  • Cytogenetics
  • Family Health
  • Female
  • Genetic Markers
  • Haplotypes
  • Humans
  • Karyotyping
  • Male
  • Oculocerebrorenal Syndrome
  • Pedigree
  • Phosphoric Monoester Hydrolases / genetics*
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • Sequence Analysis, DNA
  • X Chromosome Inactivation*


  • Genetic Markers
  • RNA, Long Noncoding
  • RNA, Untranslated
  • XIST non-coding RNA
  • Phosphoric Monoester Hydrolases
  • OCRL protein, human