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Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis.

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-Cmotif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with = 2 clinical signs/symptoms of NP-C were considered ` suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI = 70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores = 70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis.

The province of Huesca (Spain) is a traditional area for growing grapevines. There are archaeological evidences of their cultivation at least since the second century B.C. Nevertheless, in the last years the varietal diversity is markedly decreasing due to the rooting out of old plantations that are replaced with new broadly known varieties, since the market demands a certain standardization of the wine producing varieties. The objective of this study is to examine and characterise the existing varieties in the province of Huesca, mainly in vineyards planted before 1960. A total of 47 accessions were collected in 14 plots from 11 municipalities. Moreover 36 accessions from the region, planted at the Movera grapevine germplasm bank (Movera collection), located at Zaragoza (Spain) were included in the study. Ampelographic characterisation was carried out with 50 OIV descriptors for two consecutive years. Molecular characterisation was made with the following microsatellites: VVS2, VVMD5, VVMD7, VVMD27, VrZAG62 and VrZAG79. Ampelographic results were compared by cluster analysis. Most of the accessions were identified, being considered as new varieties: two white, Carrillera and Moscatel, and six red or black: Macicillo, Bomogastro, Angelina, Terrer, Parraleta Roja and Garnacha Gorda. Several new synonymies were detected, as Miguel for Vitadillo or Parrel for Trepat. Seven accessions remained unidentified. Out of the studied Vitis vinifera varieties, 23 were considered as endangered, indicating the valuable patrimony of the zone to be preserved., La provincia de Huesca (España) ha sido un lugar tradicional de cultivo de vid. Existe evidencia arqueológica de la existencia de dicho cultivo desde el siglo II a.C. Sin embargo, en las últimas décadas la diversidad varietal está disminuyendo marcadamente debido al arranque de antiguas plantaciones que están siendo reemplazadas con nuevas variedades ampliamente conocidas, ya que el mercado demanda una cierta estandarización de las variedades productoras de vino. El objetivo de este estudio es caracterizar e identificar las variedades existentes en la provincia de Huesca, principalmente en viñedos plantados antes de 1960. Se muestrearon 47 accesiones de 14 parcelas en 11 municipios. Además se incluyeron otras 36 accesiones de la provincia de Huesca que se encuentran en el banco de germoplasma de vid de Movera (colección de Movera), situado en Zaragoza (España). La caracterización ampelográfica se llevó a cabo con 50 descriptores durante dos años consecutivos. La caracterización molecular se realizó con los siguientes microsatélites: VVS2, VVMD5, VVMD7, VVMD27, VrZAG62 y VrZAG79. Los resultados ampelográficos se compararon mediante análisis de enjambres. Se identificó la mayor parte de las accesiones, detectándose las siguientes variedades nuevas: dos blancas, Carrillera y Moscatel, y seis rojas o negras, Macicillo, Bomogastro, Angelina, Terrer, Parraleta Roja y Garnacha Gorda. Se detectaron varias sinonimias nuevas, como Miguel para Vitadillo o Parrel para Trepat. Siete accesiones quedaron sin identificar. De las variedades de Vitis vinifera estudiadas, 23 se consideraron en peligro de extinción, lo que indica el valioso patrimonio de la zona que debe conservarse.