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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 | 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.

Cali F.,Laboratorio Of Genetica Molecolare | Ragalmuto A.,Laboratorio Of Genetica Molecolare | Chiavetta V.,Laboratorio Of Genetica Molecolare | Calabrese G.,U.O. di Neurologia e Neurofisiopatologia Clinica e Strumentale | And 9 more authors.
Experimental and Molecular Medicine | Year: 2010

Angelman syndrome (AS) is a severe neurobehavioural disorder caused by failure of expression of the maternal copy of the imprinted domain located on 15q11-q13. There are different mechanisms leading to AS: maternal microdeletion, uniparental disomy, defects in a putative imprinting centre, mutations of the E3 ubiquitin protein ligase (UBE3A) gene. However, some of suspected cases of AS are still scored negative to all the latter mutations. Recently, it has been shown that a proportion of negative cases bear large deletions overlapping one or more exons of the UBE3A gene. These deletions are difficult to detect by conventional gene-scanning methods due to the masking effect by the non-deleted allele. In this study, we have used for the first time multiplex ligation-dependent probe amplification (MLPA) and comparative multiplex dosage analysis (CMDA) to search for large deletions affecting the UBE3A gene. Using this approach, we identified a novel causative deletion involving exon 8 in an affected sibling. Based on our results, we propose the use of MLPA as a fast, accurate and inexpensive test to detect large deletions in the UBE3A gene in a small but significant percentage of AS patients.

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