Mitochondrial DNA heteroplasmy of the m.3243A > G mutation in maternally inherited diabetes and deafness

Cataldo, LR; Olmos, P; Smalley SV; Diez, A.; parada, a; Gejman, R; Fadic, R; Santos, JL

Abstract

Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion of mutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification of MIDD allows a correct treatment with insulin avoiding drugs that may interfere with mitochondrial electron chain transport. We estimated the degree of heteroplasmy of the mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a female adult patient. For this purpose, PCR products were inserted in a vector creating plasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to create a calibration curve used to interpolate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biological sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Más información

Título según WOS: Mitochondrial DNA heteroplasmy of the m.3243A > G mutation in maternally inherited diabetes and deafness
Título de la Revista: REVISTA MEDICA DE CHILE
Volumen: 141
Número: 3
Editorial: SOC MEDICA SANTIAGO
Fecha de publicación: 2013
Página de inicio: 305
Página final: 312
Idioma: Spanish
Notas: ISI