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X-Linked Emery-Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation With Clinical Phenotypes in Female Carriers


X-Linked Emery-Dreifuss Muscular Dystrophy: Study Of X-Chromosome Inactivation and Its Relation With Clinical Phenotypes in Female Carriers

Emanuela Viggiano et al. Genes (Basel).


X-linked Emery-Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers-25 familial and 5 sporadic cases-seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

Keywords: Emery–Dreifuss muscular dystrophy (EDMD1); X-chromosome inactivation (XCI); cardiac symptoms; skewed X-chromosome inactivation.

Conflict of interest statement

The authors declare no conflict of interest


Figure 1
Figure 1
Gene scanner traces for HpaII digested (+) and undigested (−) DNA. The peak represents the amplified androgen receptor (AR) allele. The size of the allele is determined by the number of repeats within the AR gene. The area under the peak indicates the degree of amplification of the alleles. The higher peaks correspond to the expected size of alleles, while the shorter peaks should be considered as artifacts. One carrier (A) presented a skewed XCI (20:80), while the other showed a random X-chromosome invitation (XCI) (B). The digested DNA sample of the Emery–Dreifuss muscular dystrophy (EDMD1) male (C) did not show a peak (negative control), while the undigested sample presented one peak.
Figure 2
Figure 2
Pedigree of EDMD1 families. Please note that only carriers included in the study are shown.
Figure 3
Figure 3
Distribution of XCI ratios in EDMD1 carriers. Normal distribution of the XCI pattern in the leukocytes from the analyzed EDMD1 carriers.

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