Related Experiment Video

Updated: May 21, 2026

In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
10:16

In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease

Published on: December 20, 2017

X-inactivation in Fabry disease

Deborah Elstein1, Ella Schachamorov, Rachel Beeri

  • 1Gaucher Clinic, Shaare Zedek Medical Center, Hebrew University, Hadassah Medical School, Ein Karem, Jerusalem, Israel. elstein@szmc.org.il

Gene
|June 20, 2012
PubMed
Abstract

Insights

In Fabry disease, X-chromosome inactivation (XCI) patterns in heterozygous females do not correlate with disease severity. This suggests other mechanisms cause symptoms in these women.

Area of Science:

  • Genetics
  • Biochemistry
  • Medical Genetics

Background:

  • Fabry disease is an X-linked lysosomal disorder.
  • X-chromosome inactivation (XCI) creates mosaicism in females, leading to variable disease expression.
  • Heterozygous females can be symptomatic, but often less severely than males.

Purpose of the Study:

  • To investigate if skewed X-chromosome inactivation (XCI) favoring the mutant allele occurs in female Fabry disease heterozygotes.
  • To explore the relationship between XCI patterns and clinical manifestations in these patients.

Main Methods:

  • Physical examinations and severity scoring using the Mainz Severity Score Index (MSSI).
  • Assays for α-galactosidase A enzymatic activity and mutation analysis.
  • Determination of XCI ratios from peripheral blood leukocyte samples.

Main Results:

  • Only 18.2% of samples showed highly skewed XCI (80/20 ratio).
  • No significant correlations were found between XCI ratios and age, enzyme activity, MSSI scores, or specific clinical signs (cardiac, pain, proteinuria).
  • Highly skewed XCI was less frequent in samples with nonsense mutations (14.3%).

Conclusions:

  • The observed XCI patterns in female Fabry heterozygotes are similar to the general female population.
  • The findings raise questions about the underlying mechanisms driving symptomatic disease expression in heterozygous females.
  • Further research is needed to understand the factors contributing to phenotypic variability in female Fabry disease patients.

More Related Videos

Combined DNA-RNA Fluorescent In situ Hybridization (FISH) to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells15:54

Combined DNA-RNA Fluorescent In situ Hybridization (FISH) to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells

Published on: June 14, 2014

In Vivo Modeling of the Morbid Human Genome using Danio rerio12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Related Concept Videos

X-inactivation01:58

X-inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...