Functional splicing assay supporting that c.70 + 5G > A mutation in the MPV17 gene is disease causing.
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.
Navarro-Sastre
Aleix
A
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.
García-Silva
Maria Teresa
MT
Martín-Hernández
Elena
E
Lluch
Montserrat
M
Briones
Paz
P
Ribes
Antonia
A
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
C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins