Enza Maria Valente

..We also discuss the emerging clinical and genetic overlap between JSRDs and a growing number of distinct syndromes that share a common pathogenetic mechanism that is the loss of normal function of the primary cilium and its apparatus...

..In this Review, we discuss these topics and how these concerns affect genetic counselling...

..These data implicate a new family of proteins in the ciliopathies and further support allelism between ciliopathy disorders...

..Moreover, the identification of mutations allows early prenatal diagnosis in couples at risk, while fetal neuroimaging may remain uninformative until the late second trimester of pregnancy...

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..These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech...

..These data provide a direct molecular link between mitochondria and the pathogenesis of PD...

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..Urinary disturbances (urgency and/or incontinence) were always present, even in young patients with a short disease history...

..CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies...

..One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies...

..Hence, their significance should be kept distinct from that of homozygous/compound heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion...

..The frequency of mutations in the first positionally cloned gene, AHI1, is unknown...

..These exons encode for a region of unknown function in the extracellular domain of meckelin...

..Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified...

..15445_15467del23) which produces several aberrant mRNAs. This report expands the genotypic spectrum of PINK1 mutations, with relevant implications for molecular analysis of this gene...

..These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs...

..A milder olfactory deficit, mostly involving discrimination, can be found in asymptomatic heterozygotes, possibly indicating an underlying preclinical neurodegenerative process...

..CONCLUSIONS: The significant lod scores obtained and the absence of mutations in RDS, GUCA1A, and GUCA1B support the existence of a novel, yet unidentified gene responsible for retinal dystrophy within the chromosome 6 cluster...

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..After the first months of life, global prognosis varies considerably among JSRD subgroups, depending on the extent and severity of organ involvement...

..These findings further expand the clinical spectrum of PINK1-related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD...

..These findings support genetic heterogeneity of PTD and indicate that a novel unassigned gene is responsible for focal dystonia in this family...

..However, the pathogenetic significance of heterozygous PINK1 mutations still remains to be clarified...

..The condition we describe could be a newly recognized dystonia syndrome with parkinsonism...

..2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD...

..Our findings expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical districts that are usually spared in DYT1-PTD...

..This provides a useful framework for genetic testing strategies and prediction of which patients are most likely to experience development of systemic complications...

..PARK6 appears to be an important locus for early-onset parkinsonism in European Parkin-negative patients...

..The 3 Hz protocol was well tolerated and showed good sensitivity and reproducibility. Furthermore, this test might be suitable for genotype-phenotype correlation studies...

..We think that muscle biopsy is a valuable procedure to improve diagnostic assesement in children with congenital ataxia or other undefined forms of later onset childhood ataxia associated to cerebellar atrophy at MRI...

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..These findings are opening novel interesting perspectives to identify critical molecular pathways leading to neurodegeneration...

..The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect...

..Our findings suggest that ARHSP-TCC is the most frequent form of ARHSP in Mediterranean countries and that it is particularly frequent in Italy...

..We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting...

..The mother, heterozygote for W437X mutation, was affected by Parkinson's disease and 3 further relatives were reported affected, according to an autosomal dominant transmission...

..However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia...

..Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs...

..To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis...

..Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP...

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..Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified...

..Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit...

..These findings suggest that primary familial adult-onset BSP is a distinct entity among inherited PTD and is caused by a novel, unmapped gene...

..These data suggest that further examination is warranted of the role genetic variability at this locus plays in the risk for primary dystonia...

..We conclude that deep brain stimulation can be an effective and safe treatment for MDS...

..Finally, some CM-AVM patients had neural tumors reminiscent of neurofibromatosis type 1 or 2. This is the first extensive study on the phenotypes associated with RASA1 mutations, and unravels their wide heterogeneity...

..This study shows the benefits of pallidal DBS for the dystonia of PKAN patients...

..Neither false positive nor false negative results were obtained. This multistep method can be considered a fast and reliable diagnostic strategy for the detection of EXT1/2 mutations, with excellent sensitivity and specificity...