title: Genomic and transcription studies as diagnostic tools for a prenatal detection of X-linked dilated cardiomyopathy due to a dystrophin gene mutation.
abstract: X-linked dilated cardiomyopathy (XLDC) represents a form of dystrophinopathy with exclusive heart involvement. Here a prenatal diagnosis of this condition performed in a family with XLDC is described. In this family, the causative mutation was a pure intronic deletion, which induces the splicing of a novel, aberrant, and out-of-frame exon into the dystrophin transcript. The genetic test was performed by defining both the DNA (villous) and the RNA (amniocyte) configuration. The prenatal diagnosis determined that the fetus was female, and a carrier of the genomic deletion. RNA analysis on cultured amniocytes revealed the presence of an easily detectable dystrophin transcript, as well as the co-existence of both the wild-type and the abnormal splicing profile. Our analysis represents the first report of a prenatal diagnosis in XLDC and also indicates the feasibility of dystrophin mutation detection on RNA from amniocytes. This finding suggests that the dystrophin splicing pattern in amniocytes and skeletal muscle is similar, and that, therefore, this approach could be used in other prenatal dystrophin mutation detection, where abnormal RNA splicing is thought to play a role, or for specific cases in which no mutations have been identified in the coding regions.
authors.affiliation: Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Genetica Medica, Università di Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rimessi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Laurence
authors.initials: L
authors.lastname: Duprez
authors.forename: Pietro
authors.initials: P
authors.lastname: Spitali
authors.forename: Marcella
authors.initials: M
authors.lastname: Neri
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Elisa
authors.initials: E
authors.lastname: Calzolari
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D016189:Dystrophin; D012313:RNA; D004247:DNA