title: Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene: description of an alternative MPV17 spliced form.
abstract: It has recently been reported that mutations in MPV17 gene may be causative of mtDNA depletion syndrome (MDS). Patients with this alteration presented with severe liver failure, hypoglycemia, growth retardation and neurological symptoms during the first year of life. We report on the clinical, biochemical and molecular findings of a patient presenting with lethal hepatopathy, polyneuropathy, neurological regression and leukodystrophy associated with mutations in MPV17. Mitochondrial respiratory chain activities were low in liver and within reference values in muscle. However, levels of mtDNA were markedly reduced both in muscle and liver. A novel homozygous mutation in MPV17, c.70+5G>A (IVS1+5G>A), was identified. This intronic change causes the full-length cDNA loss, probably due to loss of strength of the splice donor site of exon 1. Western blot analysis, performed in liver homogenates, further corroborates these results as the amount of patient's protein was highly reduced, or almost absent, compared with that of controls. We also identified an additional alternative spliced form in controls and in the patient, due to exon 2 skipping, that has not previously been reported.
authors.affiliation: Division of Inborn Errors of Metabolism (IBC), Department of Biochemistry and Molecular Genetics, Hospital Clinic and CIBERER, Edifici Helios III, planta baja, C/ Mejía Lequerica s/n, 08028 Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Navarro-Sastre
authors.forename: Elena
authors.initials: E
authors.lastname: Martín-Hernández
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
authors.forename: Ester
authors.initials: E
authors.lastname: Quintana
authors.forename: Enrique
authors.initials: E
authors.lastname: Medina
authors.forename: Rogelio Simón
authors.initials: RS
authors.lastname: de Las Heras
authors.forename: Montserrat
authors.initials: M
authors.lastname: Lluch
authors.forename: Alberto
authors.initials: A
authors.lastname: Muñoz
authors.forename: Pilar
authors.initials: P
authors.lastname: del Hoyo
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martín
authors.forename: Laura
authors.initials: L
authors.lastname: Gort
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D017398:Alternative Splicing; D005091:Exons; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008107:Liver Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
chemical_list: C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins