Show simple item record

dc.contributor.authorScionti, Isabella
dc.contributor.authorGreco, Francesca
dc.contributor.authorRicci, Giulia
dc.contributor.authorGovi, Monica
dc.contributor.authorArashiro, Patricia
dc.contributor.authorVercelli, Liliana
dc.contributor.authorBerardinelli, Angela
dc.contributor.authorAngelini, Corrado
dc.contributor.authorAntonini, Giovanni
dc.contributor.authorCao, Michelangelo
dc.contributor.authorDi Muzio, Antonio
dc.contributor.authorMoggio, Maurizio
dc.contributor.authorMorandi, Lucia
dc.contributor.authorRicci, Enzo
dc.contributor.authorRodolico, Carmelo
dc.contributor.authorRuggiero, Lucia
dc.contributor.authorSantoro, Lucio
dc.contributor.authorSiciliano, Gabriele
dc.contributor.authorTomelleri, Giuliano
dc.contributor.authorTrevisan, Carlo Pietro
dc.contributor.authorGalluzzi, Giuliana
dc.contributor.authorWright, Woodring E.
dc.contributor.authorZatz, Mayana
dc.contributor.authorTupler, Rossella
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:30:40Z
dc.date.available2022-08-23T17:30:40Z
dc.date.issued2012-04-06
dc.date.submitted2014-01-25
dc.identifier.citationScionti I, Greco F, Ricci G, Govi M, Arashiro P, Vercelli L, Berardinelli A, Angelini C, Antonini G, Cao M, Di Muzio A, Moggio M, Morandi L, Ricci E, Rodolico C, Ruggiero L, Santoro L, Siciliano G, Tomelleri G, Trevisan CP, Galluzzi G, Wright W, Zatz M, Tupler R. Large-scale population analysis challenges the current criteria for the molecular diagnosis of fascioscapulohumeral muscular dystrophy. Am J Hum Genet. 2012 Apr 6;90(4):628-35. doi:10.1016/j.ajhg.2012.02.019. <a href="http://dx.doi.org/10.1016/j.ajhg.2012.02.019">Link to article on publisher's site</a>
dc.identifier.issn0002-9297 (Linking)
dc.identifier.doi10.1016/j.ajhg.2012.02.019
dc.identifier.pmid22482803
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50562
dc.description.abstractFacioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causally linked to reduced numbers (≤8) of 3.3 kilobase D4Z4 tandem repeats at 4q35. However, because individuals carrying D4Z4-reduced alleles and no FSHD and patients with FSHD and no short allele have been observed, additional markers have been proposed to support an FSHD molecular diagnosis. In particular a reduction in the number of D4Z4 elements combined with the 4A(159/161/168)PAS haplotype (which provides the possibility of expressing DUX4) is currently used as the genetic signature uniquely associated with FSHD. Here, we analyzed these DNA elements in more than 800 Italian and Brazilian samples of normal individuals unrelated to any FSHD patients. We find that 3% of healthy subjects carry alleles with a reduced number (4-8) of D4Z4 repeats on chromosome 4q and that one-third of these alleles, 1.3%, occur in combination with the 4A161PAS haplotype. We also systematically characterized the 4q35 haplotype in 253 unrelated FSHD patients. We find that only 127 of them (50.1%) carry alleles with 1-8 D4Z4 repeats associated with 4A161PAS, whereas the remaining FSHD probands carry different haplotypes or alleles with a greater number of D4Z4 repeats. The present study shows that the current genetic signature of FSHD is a common polymorphism and that only half of FSHD probands carry this molecular signature. Our results suggest that the genetic basis of FSHD, which is remarkably heterogeneous, should be revisited, because this has important implications for genetic counseling and prenatal diagnosis of at-risk families.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22482803&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322229/pdf/main.pdf
dc.subjectAdult
dc.subjectAged
dc.subjectBrazil
dc.subjectChromosomes, Human, Pair 4
dc.subjectFemale
dc.subjectGenetic Testing
dc.subjectHaplotypes
dc.subjectHumans
dc.subjectItaly
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMuscular Dystrophy, Facioscapulohumeral
dc.subjectPolymorphism, Genetic
dc.subjectTandem Repeat Sequences
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.subjectMusculoskeletal Diseases
dc.subjectNervous System Diseases
dc.titleLarge-scale population analysis challenges the current criteria for the molecular diagnosis of fascioscapulohumeral muscular dystrophy
dc.typeJournal Article
dc.source.journaltitleAmerican journal of human genetics
dc.source.volume90
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wellstone_pubs/13
dc.identifier.contextkey5020592
html.description.abstract<p>Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causally linked to reduced numbers (≤8) of 3.3 kilobase D4Z4 tandem repeats at 4q35. However, because individuals carrying D4Z4-reduced alleles and no FSHD and patients with FSHD and no short allele have been observed, additional markers have been proposed to support an FSHD molecular diagnosis. In particular a reduction in the number of D4Z4 elements combined with the 4A(159/161/168)PAS haplotype (which provides the possibility of expressing DUX4) is currently used as the genetic signature uniquely associated with FSHD. Here, we analyzed these DNA elements in more than 800 Italian and Brazilian samples of normal individuals unrelated to any FSHD patients. We find that 3% of healthy subjects carry alleles with a reduced number (4-8) of D4Z4 repeats on chromosome 4q and that one-third of these alleles, 1.3%, occur in combination with the 4A161PAS haplotype. We also systematically characterized the 4q35 haplotype in 253 unrelated FSHD patients. We find that only 127 of them (50.1%) carry alleles with 1-8 D4Z4 repeats associated with 4A161PAS, whereas the remaining FSHD probands carry different haplotypes or alleles with a greater number of D4Z4 repeats. The present study shows that the current genetic signature of FSHD is a common polymorphism and that only half of FSHD probands carry this molecular signature. Our results suggest that the genetic basis of FSHD, which is remarkably heterogeneous, should be revisited, because this has important implications for genetic counseling and prenatal diagnosis of at-risk families.</p>
dc.identifier.submissionpathwellstone_pubs/13
dc.contributor.departmentProgram in Gene Function and Expression
dc.contributor.departmentWellstone Center for FSHD
dc.source.pages628-35


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record