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PubMed | Laboratorio Of Genetica Molecolare, UO Genetica Medica, Cervello, University of Palermo and 4 more.
Type: | Journal: European journal of medical genetics | Year: 2016

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more caf au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using American College of Medical Genetics and Genomics guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.


PubMed | Armenian National Academy of Sciences, National Museum of Natural History, Heritage Foundation, University of Santiago de Compostela and 67 more.
Type: Historical Article | Journal: Nature | Year: 2014

We sequenced the genomes of a 7,000-year-old farmer from Germany and eight 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations deep relationships and show that early European farmers had 44% ancestry from a basal Eurasian population that split before the diversification of other non-African lineages.


PubMed | Oxford Genetics, Medical University-Sofia, Medical University of Warsaw, University of Edinburgh and 13 more.
Type: Journal Article | Journal: Current biology : CB | Year: 2015

Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1-7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8-11]. Here, using recently described haplotype-based techniques [11], we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200 CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1,500 years are likely to have maintained differentiation among groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia.


Cannas A.,University of Cagliari | Borghero G.,University of Cagliari | Floris G.L.,University of Cagliari | Solla P.,University of Cagliari | And 21 more authors.
Neurogenetics | Year: 2013

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD. © 2013 Springer-Verlag Berlin Heidelberg.


Bianca S.,Centro Of Consulenza Genetica E Of Teratologia Della Riproduzione | Barrano B.,Centro Of Consulenza Genetica E Of Teratologia Della Riproduzione | Cutuli N.,Laboratorio Of Genetica Molecolare | Indaco L.,Centro Of Consulenza Genetica E Of Teratologia Della Riproduzione | And 4 more authors.
Fertility and Sterility | Year: 2010

Our study does not support the reported association between APOE and recurrent pregnancy loss (RPL) than the clinical management of these patients should not be influenced by the presence or not of APO E polymorphisms. © 2010 American Society for Reproductive Medicine.


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.


Cali F.,Laboratorio Of Genetica Molecolare | Ruggeri G.,Laboratorio Of Genetica Molecolare | Vinci M.,Laboratorio Of Genetica Molecolare | Vinci M.,University of Palermo | And 10 more authors.
Experimental and Molecular Medicine | Year: 2010

A consistent finding of many studies describing the spectrum of mutant phenylalanine hydroxylase (PAH) alleles underlying hyperphenylalaninemia is the impossibility of achieving a 100% mutation ascertainment rate using conventional gene-scanning methods. These methods include denaturing gradient gel electrophoresis (DGGE), denaturing high performance liquid chromatography (DHPLC), and direct sequencing. In recent years, it has been shown that a significant proportion of undetermined alleles consist of large deletions overlapping one or more exons. These deletions have been difficult to detect in compound heterozygotes using gene-scanning methods due to a masking effect of the non-deleted allele. To date, no systematic search has been carried out for such exon deletions in Italian patients with phenylketonuria or mild hyperphenylalaninemia. We used multiplex ligation-dependent probe amplification (MLPA), comparative multiplex dosage analysis (CMDA), and real-time PCR to search for both large deletions and duplications of the phenylalanine hydroxylase gene in Italian hyperphenylalaninemia patients. Four deletions removing different phenylalanine hydroxylase (PAH) gene exons were identified in 12 patients. Two of these deletions involving exons 4-5-6-7-8 (systematic name c.353-?-912 + ?del) and exon 6 (systematic name c.510-?-706 + ?del) have not been reported previously. In this study, we show that exon deletion of the PAH gene accounts for 1.7% of all mutant PAH alleles in Italian hyperphenylalaninemics.


Gencpinar P.,Dokuz Eylül University | Makay B.B.,Dokuz Eylül University | Gattorno M.,UO Pediatria II | Caroli F.,Laboratorio Of Genetica Molecolare | Unsal E.,Dokuz Eylül University
Turkish Journal of Pediatrics | Year: 2012

The hyperimmunoglobulinemia D syndrome (HIDS), so-called mevalonate kinase deficiency, is caused by recessive mutations in the gene encoding mevalonate kinase enzyme. HIDS is characterized by recurrent fever attacks of 3-7 days that begin in infancy and recur every 4-6 weeks. The febrile period is accompanied by lymphadenopathy, arthralgia, abdominal pain, diarrhea, aphthous ulcers, and varying degree of skin involvement. The course and severity of the disease may be quite different. There is no effective or proven therapy for HIDS. We report two cases with HIDS, which had separate clinical findings and treatment strategies.

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