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Scuderi C.,Unita Operativa di Malattie Neuromuscolari | Borgione E.,Unita Operativa di Malattie Neuromuscolari | Castello F.,Unita Operativa di Malattie Neuromuscolari | Lo Giudice M.,Unita Operativa di Malattie Neuromuscolari | And 10 more authors.
Neuromuscular Disorders | Year: 2015

Mutations in the polymerase gamma-1 (POLG1) gene, encoding the catalytic subunit of the mtDNA-specific polymerase-γ, compromise the stability of mitochondrial DNA (mtDNA) and are responsible for numerous clinical presentations as autosomal dominant or recessive progressive external ophthalmoplegia (PEO), sensory ataxia, neuropathy, dysarthria and ophthalmoparesis (SANDO), spinocerebellar ataxia with epilepsy (SCAE) and Alpers syndrome.POLG1 mutations result in extremely heterogeneous phenotypes which often have overlapping clinical findings, making it difficult to categorize patients into syndromes, and genotype-phenotype correlations are still unclear.We describe a new family with a particular spectrum of clinical signs, that carried the c.752C>T mutation in exon 3 (T251I) and the c.1760C>T in exon 10 (P587L) in cis. These mutations were associated in the proband and in her brother with the new probably pathogenic mutation c.347C>A in exon 2 (P116Q).The proband presented a progressive cognitive impairment, mild myopathy, dilated cardiac right atrium and posterior white matter mild signal alteration, while her brother had migraine, mild myopathy, palpebral ptosis and posterior white matter mild signal alteration. Their mother and their sister carried the in cis T251I and the P587L mutations. The first presented neurosensorial hypoacusia, fatigue, heart block and a cerebral arteriovenous malformation nidus, while the latter had borderline intellectual functioning and signs of muscular involvement. Their father, with the P116Q mutation, had diabetes and myopathy.The complexity of the genotype-phenotype correlations associated with POLG1 mutations is reinforced in this work as evidenced by the presence of different clinic features in patients carrying the same mutations. © 2015 Elsevier B.V.. Source


Scuderi C.,Unita Operativa di Malattie Neuromuscolari | Borgione E.,Unita Operativa di Malattie Neuromuscolari | Castello F.,Unita Operativa di Malattie Neuromuscolari | Giudice M.L.,Unita Operativa di Malattie Neuromuscolari | And 9 more authors.
Mitochondrion | Year: 2010

We describe a 16-year-old girl with mental retardation, myoclonic epilepsy, ataxia, mitochondrial myopathy, sensorineural hearing loss, lactic acidosis, and MRI evidence of diffuse subcortical laminar heterotopia and agyria/pachygyria. Restriction fragment length polymorphism (RFLP) and DNA sequence analyses revealed two pathogenic mutations: a heteroplasmic m.3243A > G in muscle and blood, and a new heterozygous insertion at nt697 in the doublecortin gene (DCX), resulting in a frameshift after amino acid residue 232, with a premature stop codon at amino acid residue 244. This is yet another example of genetic " double trouble" resulting in a complex phenotype. © 2010 Mitochondria Research Society. Source


Borgione E.,Unita Operativa di Malattie Neuromuscolari | Lo Giudice M.,Unita Operativa di Malattie Neuromuscolari | Castello F.,Unita Operativa di Malattie Neuromuscolari | Musumeci S.A.,Unita Operativa di Neurologia per il Ritardo Mentale | And 9 more authors.
Neurological Sciences | Year: 2013

A deletion of one of the two copies of the 9-bp tandem repeat sequence (CCCCCTCTA), in the small non-coding/untranslated segment located between the cytochrome oxidase II and lysine tRNA genes of mitochondrial DNA (mtDNA), has previously been used as a polymorphic anthropological marker (MIC9D) for people of Africa and Asia, but it has been rarely reported in Europe. 32 Sicilian patients with syndromic hearing loss, negative for mutations in GJB2 and GJB6 genes, were tested for mtDNA known point mutations associated with syndromic or non-syndromic hearing loss by RFLP and/or direct sequencing. We identified the presence of the MIC9D in homoplasmy in lymphocytes and muscle of three subjects with sensorineural hearing loss and encephalomyopathy, two of these also presented moderate mental retardation. This deletion was absent in 300 Caucasian controls. Although further studies are warranted, our results suggest that the MIC9D polymorphism could have a susceptibility role in Caucasus, such as Sicily population. © 2013 Springer-Verlag Italia. Source

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