期刊
JOURNAL OF THE NEUROLOGICAL SCIENCES
卷 399, 期 -, 页码 69-75出版社
ELSEVIER
DOI: 10.1016/j.jns.2019.02.010
关键词
Leigh syndrome; Complex I deficiency; ND3 gene; mtDNA
资金
- grant MITO-NEXT Conto capitale from the Italian Ministry of Health
- grant Ricerca Corrente 5x1000 2016-2017 from the Italian Ministry of Health
Complex I (CI) is the largest component of the mitochondrial respiratory chain (MRC) and it is made up of 7 mitochondria] DNA (mtDNA)-encoded and at least 38 nuclear DNA-encoded subunits. Isolated CI deficiency is the most common single enzyme deficiency in the heterogeneous group of MRC disorders and it is a relatively common etiology of Leigh-like syndrome (LS). With a few exceptions, descriptions of the clinical spectrum of specific mutations in CI are scarce. We here present three unrelated Italian children who harbored the homoplasmic m.10197G > A mutation in MT-ND3 associated with reduced enzyme activity of CI in muscle. Compared with the spectrum of phenotypes seen in 13 previously described families with the same mutation, these children showed some novel clinical features. Two of the boys presented with subacute onset of dystonia, which showed a remitting-relapsing clinical course in one of them. The third boy presented acute symptoms consisting of speech impairment, progressive left-sided hemiparesis, and also vertebral and arterial malformations. In all the children, molecular studies identified a similar mutation load in tissues, and neuroimaging findings were consistent with the features seen in LS. Functional investigations in cultured skin fibroblasts suggested low ATP production in homoplasmic cells. Our results confirm that the m.10197G > A mutation is relevant to these patients' clinical and biochemical phenotypes, which thus expand the array of phenotypes associated with this variant.
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