Identificazione del gene di una nuova leucodistrofia con atassia, sordità e cardiomiopatia

Oggetto: Il presente lavoro descrive una nuova entità clinica di leucodistrofia e lo studio genetico effettuato per il riconoscimento del gene responsabile. Descrizione del fenotipo clinico: Si tratta di una nuova malattia neurodegenerativa riscontrata inizialmente in 3 individui appartenenti ad una famiglia multiconsanguinea. L’esordio è precoce e caratterizzato da una sindrome atassica lentamente progressiva e spasticità. Successivamente i pazienti presentano una ipoacusia neurosensoriale, che evolve in una sordità completa. Infine sviluppano una cardiomiopatia rapidamente ingravescente, causa del decesso entro la seconda decade di vita. La risonanza magnetica evidenzia alterazioni diffuse della sostanza bianca nelle sequenze T2 pesate. Un estensivo screening neurometabolico ha evidenziato unicamente un lieve incremento dei valori degli enzimi epatici. Caratterizzazione genetica: Per ricercare il gene responsabile di questa nuova condizione clinica, è stato effettuato uno studio di linkage. Mediante l’utilizzo di 384 primers, è stato analizzato l’intero genoma dei 3 probandi, attraverso la tecnica del DNA pooling, che ha consentito di selezionare 21 regioni candidate. Inserendo tutti i primers informativi, analizzando l’intera famiglia, e attraverso lo studio di analisi dell’aplotipo, è stato identificato il locus sul braccio corto del cromosoma 1 (1p34). Tramite sequenza diretta, sono state analizzate le porzioni codificanti di tutti i geni presenti all’interno della regione e le loro sequenze introniche fiancheggianti. E’ stata così trovata una mutazione puntiforme missenso, non rilevata nella popolazione generale, responsabile della sindrome. Sono stati individuati, successivamente, altri 4 pazienti, con caratteristiche cliniche sovrapponibili, non legati alla nostra famiglia, con una variante della stessa mutazione.Object: This paper described a new clinical entity of leukodistrophy and the genetic study for gene’s identification. Clinical phenotype: We reported initially three patients, from a large consanguineous family, showing a distinctive white matter disease, at early onset, with a clinical phenotype characterized by slowly progressive cerebellar ataxia and spasticity. Liver enzymes were elevated in the patients, but extensive neurometabolic studies failed to detect any specific biochemical abnormalities. As this disease progressed, all patients experienced sensory-neural deafness, resulting in complete hearing loss, and developed a restrictive cardiomyopathy after the age of 13 years and leading to death in two cases. In the three propositi, brain MRI showed a diffuse abnormal white matter signal on T2-weighted images . Genetical descriptions: Aiming at the identification of the specific gene, we performed a genomewide linkage analysis in affected and not-affected members of this first family. Due to the high consanguinity, we initially used the DNA pooling method to look for the region of homozygosity. Using a set of microsatellite markers distributed along the 22 autosomes, we detected initially 21 candidate regions. Extending the analysis to individual DNA from the non affected siblings, and using additional markers, we found a likely region of homozygosity on chromosome 1p34.3-p33. We analyzed the coding sequence and flanking intronic regions of these genes, and we found a missence mutation liable to this leuckodistrophy. In the same time, we analysed a second consanguineous family in which the same clinical phenotype was present. The sequencing of the genes allowed finding 2 homozygote variations in gene ADCL for the 2 families

Validation of the Concise Assessment Scale for Children’s Handwriting (BHK) in an Italian Population

Handwriting difficulties represent a common complaint among children and may cause a significant delay in motor skills achievement. The Concise Assessment Scale for Children’s Handwriting (BHK) assesses handwriting skill in clinical and experimental settings, providing a quick evaluation of handwriting quality and speed through a copying text. The aim of the present study was to validate the Italian adaptation of the BHK in a representative primary school population. Overall, 562 children aged 7–11 from 16 public primary schools of Rome were included and asked to copy a text in 5 min using cursive handwriting. Handwriting quality and copying speed were measured. The included population followed a normal distribution for the BHK quality scores. Sex influenced the total quality scores, whereas school level influenced the copying speed. The BHK quality score was higher in girls (p < 0.05) and resulted as a stable parameter along the school years, without significant variations with regard to the years spent in handwriting exercise (p = 0.76). The handwriting speed was influenced by school level, and significant differences were found for each of the grades from the second to the fifth (p < 0.05), but not for gender (p = 0.47). Both BHK measures represent a helpful tool for the characterization and assessment of children with handwriting difficulties. The present study confirms that sex influences total BHK quality score, while school level influences handwriting speed

Validation of the Concise Assessment Scale for Children’s Handwriting (BHK) in an Italian Population

Handwriting difficulties represent a common complaint among children and may cause a significant delay in motor skills achievement. The Concise Assessment Scale for Children’s Handwriting (BHK) assesses handwriting skill in clinical and experimental settings, providing a quick evaluation of handwriting quality and speed through a copying text. The aim of the present study was to validate the Italian adaptation of the BHK in a representative primary school population. Overall, 562 children aged 7–11 from 16 public primary schools of Rome were included and asked to copy a text in 5 min using cursive handwriting. Handwriting quality and copying speed were measured. The included population followed a normal distribution for the BHK quality scores. Sex influenced the total quality scores, whereas school level influenced the copying speed. The BHK quality score was higher in girls (p p = 0.76). The handwriting speed was influenced by school level, and significant differences were found for each of the grades from the second to the fifth (p p = 0.47). Both BHK measures represent a helpful tool for the characterization and assessment of children with handwriting difficulties. The present study confirms that sex influences total BHK quality score, while school level influences handwriting speed