Skewed X-chromosome inactivation plays a crucial role in the onset of symptoms in carriers of Becker muscular dystrophy.
BACKGROUND
Becker muscular dystrophy (BMD) is an X-linked recessive disorder affecting approximately 1: 18.000 male births. Female carriers are usually asymptomatic, although 2.5-18% may present muscle or heart symptoms. In the present study, the role of the X chromosome inactivation (XCI) on the onset of symptoms in BMD carriers was analysed and compared with the pattern observed in Duchenne muscular dystrophy (DMD) carriers.


METHODS
XCI was determined on the lymphocytes of 36 BMD carriers (both symptomatic and not symptomatic) from 11 families requiring genetic advice at the Cardiomyology and Medical Genetics of the Second University of Naples, using the AR methylation-based assay. Carriers were subdivided into two groups, according to age above or below 50 years. Seven females from the same families known as noncarriers were used as controls. A Student's t-test for nonpaired data was performed to evaluate the differences observed in the XCI values between asymptomatic and symptomatic carriers, and carriers aged above or below 50 years. A Pearson correlation test was used to evaluate the inheritance of the XCI pattern in 19 mother-daughter pairs.


RESULTS
The results showed that symptomatic BMD carriers had a skewed XCI with a preferential inactivation of the X chromosome carrying the normal allele, whereas the asymptomatic carriers and controls showed a random XCI. No concordance concerning the XCI pattern was observed between mothers and related daughters.


CONCLUSIONS
The data obtained in the present study suggest that the onset of symptoms in BMD carriers is related to a skewed XCI, as observed in DMD carriers. Furthermore, they showed no concordance in the XCI pattern inheritance.
Cardiomiology and Medical Genetics, Department of Experimental Medicine, University of Campania, Naples, Italy.
Emanuela
E
Viggiano
Cardiomiology and Medical Genetics, Department of Experimental Medicine, University of Campania, Naples, Italy.
Esther
E
Picillo
Cardiomiology and Medical Genetics, Department of Experimental Medicine, University of Campania, Naples, Italy.
Manuela
M
Ergoli
Section of Biotechnology and Molecular Biology 'A. Cascino', Department of Experimental Medicine, University of Campania, Naples, Italy.
Alessandra
A
Cirillo
Section of Biotechnology and Molecular Biology 'A. Cascino', Department of Experimental Medicine, University of Campania, Naples, Italy.
Stefania
S
Del Gaudio
Cardiomiology and Medical Genetics, Department of Experimental Medicine, University of Campania, Naples, Italy.
Luisa
http://orcid.org/0000-0002-0925-7158
L
Politano
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D049951:X Chromosome Inactivation; D055815:Young Adult
D016189:Dystrophin
Becker-manifesting carriers; X-chromosome inactivation; skewed X-chromosome inactivation