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Clinical features of MELAS and its relation with A3243G gene point mutation
Jin Zhang1, Junhong Guo1, Wanghui Fang1
1Department of Internal Medicine-Neurology, The First Hospital of Shanxi Medical University Taiyuan 030001, Shanxi, China.
Abstract:
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) mostly occur in children. The point mutation A3243G of mitochondrial DNA (mtDNA) may work as a specific bio-marker for mitochondrial disorders. The related clinical features, however, may vary among individuals. This study therefore investigated the relation between MELAS clinical features and point mutation A3243G of mtDNA, in an attempt to provide further evidences for genetic diagnosis of MELAS. Children with MELAS-like syndromes were tested for both blood lactate level and point mutation A3243G of mtDNA. Further family study was performed by mtDNA mutation screening at the same loci for those who had positive gene mutation at A3243G loci. Those who were negative for A3243G point mutation were examined by muscle biopsy and genetic screening. Both clinical and genetic features were analyzed. In all 40 cases with positive A3243G mutation, 36 children fitted clinical diagnosis of MELAS. In other 484 cases with negative mutation, only 8 children were clinically diagnosed with MELAS. Blood lactate levels in both groups were all elevated (P>0.05). In a further genetic screening of 28 families, 10 biological mothers and 8 siblings of MELAS children had positive A3243G point mutations but without any clinical symptoms. Certain difference existed in the clinical manifestations between children who were positive and negative for A3243G mutation of mtDNA but without statistical significance. MELAS showed maternal inheritance under most circumstances.
Insights
The A3243G point mutation in mitochondrial DNA (mtDNA) is a key biomarker for mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). This mutation is often maternally inherited, even in asymptomatic family members.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Biology
Background:
- Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) is a significant pediatric disorder.
- The A3243G point mutation in mitochondrial DNA (mtDNA) is a recognized biomarker for mitochondrial disorders.
- Clinical presentations of MELAS can be highly variable among affected individuals.
Purpose of the Study:
- To investigate the correlation between specific clinical features of MELAS and the A3243G point mutation in mtDNA.
- To provide additional evidence supporting the genetic diagnosis of MELAS.
- To analyze clinical and genetic characteristics in children with MELAS-like syndromes.
Main Methods:
- Genetic screening for the A3243G point mutation in mtDNA.
- Measurement of blood lactate levels.
- Muscle biopsy and genetic screening for cases negative for the A3243G mutation.
- Family-based genetic screening for maternal inheritance patterns.
Main Results:
- Out of 40 cases with the A3243G mutation, 36 met the clinical diagnosis for MELAS.
- Among 484 cases negative for the A3243G mutation, only 8 were clinically diagnosed with MELAS.
- Elevated blood lactate levels were observed in both mutation-positive and mutation-negative groups.
- The A3243G mutation was identified in asymptomatic mothers and siblings, indicating maternal inheritance.
Conclusions:
- The A3243G point mutation is strongly associated with MELAS diagnosis.
- While clinical features may differ, the A3243G mutation is a crucial diagnostic marker.
- MELAS predominantly exhibits maternal inheritance patterns.
- Genetic screening for the A3243G mutation is vital for diagnosing MELAS and identifying at-risk family members.
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