title: Functional splicing assay supporting that c.70 + 5G > A mutation in the MPV17 gene is disease causing.
abstract: Mitochondrial DNA depletion syndrome (MDS) is a group of disorders characterized by a quantitative reduction of the mitochondrial DNA copy number and inherited as autosomal recessive traits. Patients affected by this group of diseases present with a wide variety of symptoms depending on the altered gene. MPV17 is one of the genes causing combined encephalopathy and liver failure and at present there is no treatment for this devastating disease. The gene codes for an inner mitochondrial membrane protein, but its function is still unknown, and therefore, the only way to offer prenatal diagnosis relies on DNA studies. Consequently, mutations have to be well characterized. We previously described a patient homozygous for a novel intronic mutation in the MPV17 gene (c.70 + 5G > A). Here we report the use of a functional splicing assay based on the use of minigenes to support that c.70 + 5G > A mutation is disease causing. We carried out three prenatal diagnoses on three consecutive pregnancies of the previously described family. After two affected fetuses, a healthy baby was born homozygous for the wild-type allele.
authors.affiliation: Sección de Errores Congénitos del Metabolismo, IBC, Servicio de Bioquímica y Genética Molecular and CIBER de Enfermedades Raras, Hospital Clínic, Edificio Helios III, 08028 Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Navarro-Sastre
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: García-Silva
authors.forename: Elena
authors.initials: E
authors.lastname: Martín-Hernández
authors.forename: Montserrat
authors.initials: M
authors.lastname: Lluch
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D002478:Cells, Cultured; D017809:Fatal Outcome; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000235:genetics*; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007223:Infant; D050498:Live Birth; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D011296:Prenatal Diagnosis / Q000379:methods*; D012326:RNA Splicing
chemical_list: C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins