[Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness]. / Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna.

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 corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. 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 femóle adult patient. For this purpose, PCR producís were inserted in a vector creating plasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate 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 biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna / Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness

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 ofmutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification ofMIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. We estimated the degree of heteroplasmy ofthe mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a femóle adult patient. For this purpose, PCR producís were inserted in a vector creatingplasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate 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 biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Mitochondrial diabetes and deafness: possible dysfunction of strial marginal cells of the inner ear.

OBJECTIVE: Some patients with the syndrome of mitochondrial diabetes and deafness (MIDD) have a m.3243A>G mutation of the MTTL1 gene encoding transfer ribonucleic acid for the amino acid leucine (tRNALeu(UUR)). One of our MIDD patients inspired us to propose an integrated view on how a single mutation of the mitochondrial deoxyribonucleic acid (DNA) affects both the glucose metabolism and the inner ear physiology. DESIGN: (a) Study of mitochondrial DNA in a patient with MIDD. (b) REVIEW OF THE LITERATURE on the impact of the m.3243A>G mutation on glucose metabolism and on the physiology of the hearing process. SETTINGS: Outpatient diabetes and nutrition department and molecular nutrition laboratory. METHODS: (a) Polymerase chain reaction followed by restriction fragment analysis identified the m.3243A>G mutation. (b) REVIEW OF THE LITERATURE from 1994 to 2009. RESULTS: (a) Molecular study: the m.3243A>G mutation was detected with an appreciable level of heteroplasmy. (b) REVIEW OF THE LITERATURE: the strial marginal cells located near the organ of Corti fulfill two characteristics: they are rich in mitochondria, and their dysfunction may produce neurosensorial deafness by means of a reduction in the potassium ion concentration of the endolymph. CONCLUSIONS: The m.3243A>G mutation not only underlies a dysfunction of the insulin-producing beta cell of the pancreas but also results in a reduction in adenosine triphosphate production of the strial marginal cells of the inner ear, thus diminishing the energy (in the form of potassium ion gradient) needed for the outer hair cells of the organ of Corti to amplify the soundwaves, particularly at high frequencies.

Near-optimal glycemic control in Chilean women with pregestational type-2 diabetes: persistent macrosomia relates to maternal pre-pregnancy overweight.

UNLABELLED: After a 10-year program intending to improve glycemic control in diabetic pregnancies, we evaluated whether factors underlying macrosomia are similar for type-1 and -2 pregestational diabetic women. PATIENTS AND METHODS: Twenty-three pregnancies in type-1 diabetics (PDM1, age 28.3+/-1.1 years) and 51 pregnancies in type-2 diabetics (PDM2, age 32.8+/-0.6 years) were followed and treated with intensified insulin therapy. Several factors potentially influencing macrosomia were evaluated. STATISTICS: chi-square, Fisher's exact, Student's "t" and Mann-Whitney "U" tests, and ROC analysis. RESULTS: In PDM1 and PDM2, respectively, large-for-gestational-age (LGA) frequencies were 26.08% and 37.25% (NS), antepartum HbA1c values were 6.5+/-0.32 and 6.1+/-0.16 (NS), and pre-pregnancy body mass indexes (BMI) were 23.03+/-0.66 and 30.01+/-0.89 (p<0.0001). In PDM1 the main predictor of LGA was an antepartum HbA1c> or =6.8% (p=0.046), whereas in PDM2 pregestational BMI> or =24 the variable associated (p=0.032) with LGA newborns. CONCLUSIONS: PDM1 and PDM2 differ in the underlying factors related to macrosomia. Whereas in PDM1 the antepartum HbA1c emerged as the most significant variable, suggesting that glycemic control largely determines macrosomia, in PDM2 with near-optimal glycemic control, macrosomia related to pregestational BMI.