000			02758na a2200229 4500
003			H12O
005			20180113070358.0
008			130622s2012 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_9624 _aHernández Laín, Aurelio _e Anatomía Patológica
245	0	0	_aPrognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy. _h[artículo]
260			_bOrphanet Journal of Rare Diseases, _c2012
300			_a23;7:82.
500			_aFormato Vancouver: Juan-Mateu J, Rodríguez MJ, Nascimento A, Jiménez-Mallebrera C, González-Quereda L, Rivas E, et al. Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy. Orphanet J Rare Dis. 2012 Oct 23;7:82.
501			_aPMID: 23092449
504			_aContiene 41 referencias
520			_aBetween 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy. Methods: We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI) analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females. Results: Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found. Conclusions: Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene.
710			_9330 _aServicio de Anatomía Patológica
856			_uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492175/#!po=1.28205 _yAcceso libre
942			_n0 _2ddc _cART
999			_c3576 _d3576