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Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation
- Source :
- Journal of Inherited Metabolic Disease, 35, 1059-69, Journal of Inherited Metabolic Disease, 35, 6, pp. 1059-69, Journal of Inherited Metabolic Disease
- Publication Year :
- 2012
-
Abstract
- Item does not contain fulltext The m.3243A > G mutation has become known as the MELAS mutation. However, many other clinical phenotypes associated with this mutation have been described, most frequently being maternally inherited diabetes and deafness (MIDD). The m.3243A > G mutation, can be detected in virtually all tissues, however heteroplasmy differs between samples. Recent reports indicate, a preference to perform mutation analysis in urinary epithelial cells (UEC). To test this, and to study a correlation between the mutational load in different tissues with two mitochondrial scoring systems (NMDAS and NPMDS) we investigated 34 families carrying the m.3243A > G mutation. Heteroplasmy was determined in three non-invasively collected samples, namely leucocytes, UEC and buccal mucosa. We included 127 patients, of which 82 carried the m.3243A > G mutation. None of the children (n = 11) had specific complaints. In adults (n = 71), a median NMDAS score of 15 (IQR 10-24) was found. The most prevalent symptoms were hearing loss(48%), gastro-intestinal problems(42%), exercise intolerance(38%) and glucose intolerance(37%). Ten patients had neurologic involvement. Buccal mucosa had the best correlation with the NMDAS in all adults (r = 0.437,p < 0.001), whereas UEC had the strongest correlation with the NMDAS in severely affected patients (r = 0.593,p = 0.002). Heteroplasmy declined significantly with increasing age in all three samples (leucocytes r = -0.705 (p < 0.001), UEC r = -0.374(p = 0.001), buccal mucosa r = -0.460(p < 0.001). In our cohort of 82 patients, the m.3243A > G mutation causes a wide variety of signs and symptoms, MIDD being far more prevalent than MELAS. Looking at the characteristics of the three non-invasively available tissues for testing heteroplasmy we confirm that UEC are the preferred sample to test.
- Subjects :
- Male
Saliva
Pathology
Mitochondrial Diseases
DNA Mutational Analysis
Deafness
MELAS syndrome
Gastroenterology
Cohort Studies
RNA, Transfer
MELAS Syndrome
Genetics(clinical)
Child
Genetics (clinical)
Netherlands
Aged, 80 and over
Base Composition
Mitochondrial medicine Energy and redox metabolism [IGMD 8]
Middle Aged
Heteroplasmy
Renal disorder Membrane transport and intracellular motility [IGMD 9]
Phenotype
Mitochondrial medicine [IGMD 8]
Child, Preschool
Mutation (genetic algorithm)
Female
Original Article
medicine.symptom
Adult
Heterozygote
medicine.medical_specialty
Adolescent
Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3]
Exercise intolerance
Biology
DNA, Mitochondrial
Renal disorder Energy and redox metabolism [IGMD 9]
Genomic disorders and inherited multi-system disorders [IGMD 3]
Young Adult
Diabetes mellitus
Internal medicine
Genetics
medicine
Humans
Point Mutation
Health aging / healthy living Cardiovascular diseases [IGMD 5]
Aged
Point mutation
Infant
medicine.disease
Diabetes Mellitus, Type 2
Quality of Life
Mutation testing
Subjects
Details
- ISSN :
- 01418955
- Database :
- OpenAIRE
- Journal :
- Journal of Inherited Metabolic Disease, 35, 1059-69, Journal of Inherited Metabolic Disease, 35, 6, pp. 1059-69, Journal of Inherited Metabolic Disease
- Accession number :
- edsair.doi.dedup.....21c0781f5ba9f22bad7337911cf38184