A3243G mitochondrial mutation associated with polymicrogyria

Abstract

The mitochondrial transfer ribonucleic acid for leucine is encoded by nucleotides 3230-3304. A-to-G transition at nucleotide 3243 can cause maternally transmitted diabetes mellitus-deafness syndrome, and MELAS syndrome. MELAS syndrome is a rare disorder of mitochondrial energy production, and is an acronym for myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Cortical malformations are heterogeneous and result from abnormal cell proliferation/apoptosis, migration, and/or differentiation of neuroepithelial cells. They are an important and relatively common cause of intractable epilepsy and neurodevelopmental disorders. The association between these A3243G mutations and cortical malformation has never before been reported. Here a 14-year-old female with A3243G mutation and polymicrogyria is described and possible aetiologies of this association are discussed.

Malformations of cortical development: clinical features and genetic causes

“…Pathological changes have not been defined for most of these disorders, and whether these syndromes are true polymicrogyria or polymicrogyria-like cortical malformations is usually not clear. Polymicrogyria-like cortical malformations have been reported with several metabolic diseases with severe phenotypes, including Zellweger syndrome, 130,131 neonatal adreno leukodystrophy, 113 fumaric aciduria, 75 mitochondrial diseases, 132 glutaric aciduria type 2, 133 maple-syrup-urine disease, 134 and histidinaemia. 135 However, the histopathology differs from classic polymicrogyria for several of these disorders, especially the peroxisomal disorders and glutaric aciduria type 2.…”

Genetics of the polymicrogyria syndromes

“…Both were carriers of the A3243G mutation on MTTL1. 111 Again, as these are isolated findings, further studies are required to investigate the possible importance of these genes in the development of polymicrogyria.…”

Congenital brain malformations in mitochondrial disease

“…In some cases, this may not be true polymicrogyria and the shrunken gyri may re£ect underlying degenerative changes that have interfered with subsequent development (Chow et al 1987). However, true polymicrogyria has been described in patients with fumarase de¢ciency (Kerrigan et al 2000) and in association with the common MELAS mutation (Keng et al 2003). Polymicrogyria and other forms of cortical dysplasia are also major features of Zellweger syndrome.…”