Dataset Information

A comprehensive overview of the cystic fibrosis on the island of Sao Miguel (Azores, Portugal).

ABSTRACT: BACKGROUND:Early diagnosis and treatment are improving significantly the quality of life of patients with cystic fibrosis (CF). This recessive disease is caused by a great variability of mutations in the CF transmembrane conductance (CFTR) gene, whose spectrum and frequency can be different across populations. METHODS:We performed a retrospective cross-sectional study of CF patients from the island of São Miguel (Azores, Portugal) through a clinical, genealogical, genetic and epidemiological investigation. The clinical course of patients was analyzed as a whole and according to their genotype. RESULTS:We identified 14 CF patients within a 23-year period, corresponding to a cumulative incidence of 1:3012 births, being three of them born from consanguineous unions. Genetic analysis revealed three CFTR genotypes: p.[Ser4Ter];[Gln1100Pro] was present in one patient with a less severe phenotype (1/14); c.[120del23];p.[Phe508del], a very rare one (2/14); and p.[Phe508del];[Phe508del] in the remaining patients (11/14). Clinically, respiratory infections (8/14) and growth failure (6/14) were the most common initial manifestations. All patients presented pancreatic dysfunction, with 21.4 and 100% of them showing endocrine and exocrine insufficiency, respectively. As expected, patients with severe phenotype were homozygous for p.Phe508del and had the lowest value of body mass index. CONCLUSIONS:The present study demonstrated that São Miguel Island has an increased incidence of CF when compared to recent Portuguese data (1:7500 live births). It also allowed a comprehensive overview of CF in São Miguel, improving medical practice along with genetic counselling and creating opportunities for genotype-targeted therapies.

SUBMITTER: Rosa J

PROVIDER: S-EPMC6942372 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal).

Rosa Joana J Gaspar-Silva Patrícia P Pacheco Paula P Silva Conceição C Branco Cláudia C CC Vieira Barbara S BS Carreiro Alexandra A Gonçalves Juan J Mota-Vieira Luisa L

BMC pediatrics 20200103 1

<h4>Background</h4>Early diagnosis and treatment are improving significantly the quality of life of patients with cystic fibrosis (CF). This recessive disease is caused by a great variability of mutations in the CF transmembrane conductance (CFTR) gene, whose spectrum and frequency can be different across populations.<h4>Methods</h4>We performed a retrospective cross-sectional study of CF patients from the island of São Miguel (Azores, Portugal) through a clinical, genealogical, genetic and epid ...[more]

PMID: 31900120

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Project description:BackgroundThe macroalgal flora of the Island of São Miguel (eastern group of the Azores Archipelago) has attracted the interest of many researchers in the past, the first publications going back to the nineteenth century. Initial studies were mainly taxonomic, resulting in the publication of a checklist of the Azorean benthic marine algae. Later, the establishment of the University of the Azores on the Island permitted the logistic conditions to develop both temporal studies and long-term research and this resulted in a significant increase on research directed at the benthic marine algae and littoral communities of the Island and consequent publications.Prior to the present paper, the known macroalgal flora of São Miguel Island comprised around 260 species. Despite this richness, a significant amount of the research was never made public, notably Masters and PhD theses encompassing information regarding presence data recorded at littoral and sublittoral levels down to a depth of approximately 40 m around the Island and the many collections made, which resulted in vouchers deposited in the AZB Herbarium Ruy Telles Palhinha and the LSM- Molecular Systematics Laboratory at the Faculty of Sciences and Technology of the University of the Azores.The present publication lists the macroalgal taxonomic records, together with information on their ecology and occurrence around São Miguel Island, improving the knowledge of the Azorean macroalgal flora at local and regional scales.New informationA total of 12,781 specimens (including some identified only to genus) belonging to 431 taxa of macroalgae are registered, comprising 284 Rhodophyta, 59 Chlorophyta and 88 Ochrophyta (Phaeophyceae). Of these, 323 were identified to species level (212 Rhodophyta, 48 Chlorophyta and 63 Ochrophyta), of which 61 are new records for the Island (42 Rhodophyta, 9 Chlorophyta and 10 Ochrophyta), one an Azorean endemic (Predaea feldmannii subsp. azorica Gabriel), five are Macaronesian endemisms (the red algae Botryocladia macaronesica Afonso-Carrillo, Sobrino, Tittley & Neto, Laurencia viridis Gil-Rodríguez & Haroun, Millerella tinerfensis (Seoane-Camba) S.M.Boo & J.M.Rico, Phyllophora gelidioides P.Crouan & H.Crouan ex Karsakoff and the green alga Codium elisabethiae O.C.Schmidt), 19 are introduced species (15 Rhodophyta, two Chlorophyta and two Ochrophyta) and 32 are of uncertain status (21 Rhodophyta, five Chlorophyta and six Ochrophyta).

Project description:BackgroundLeptospirosis is a worldwide zoonotic and recognized neglected infectious disease. It has been observed that only a proportion of individuals exposed to pathogenic species of Leptospira become infected and develop clinically evident disease. Moreover, little information is available in subsequent reinfections. In the present study, we determine if a first infection with leptospirosis protects against subsequent reinfection, and investigate which of the host genetic factors are involved in the susceptibility and resistance to leptospirosis.Methodology and findingsWe conducted, in 2011, a retrospective hospital-based case-control study in the São Miguel Island population (Azores archipelago). In order to determine the seropositivity against pathogenic Leptospira after the first episode of leptospirosis, we performed a serological evaluation in 97 unrelated participants diagnosed with leptospirosis between 1992 and 2011. The results revealed that 46.4% of the 97 participants have circulating anti-Leptospira antibodies, and from these participants 35.6% maintained the seroprevalence for the same serogroup. Moreover, three of them were reinfected with unrelated Leptospira serovars. The genetic study was carried out by adding a control group composed of 470 unrelated healthy blood donors, also from São Miguel Island. Twenty five SNPs among twelve innate immune genes - IL1α, IL1β, IL6, IL10, IL12RB1, TLR2, TLR4, TLR9, CD14, CISH, LTA and TNF - were genotyped, as well as HLA class I (-A and -B) genes. Association analysis indicates that genotypes -511GG (OR=1.6, 95%CI 1.01-2.56, p=0.04) in IL1β, +1196CG (OR=2.0, 95%CI 1.26-3.27, p=0.003) in IL12RB1, -292TA (OR=1.8, 95% CI 1.06-2.1, p=0.03) and +3415CG (OR=1.8, 95% CI 1.08-3.08, p=0.02), both in CISH confer susceptibility to pathogenic Leptospira.ConclusionThe present study suggests some degree of long-term protection against leptospires with an attenuation of symptoms in case of reinfection. Moreover, our data supports the genetic influence of IL1β, IL12RB1 and CISH genes and the susceptibility to leptospirosis infection.

Project description:Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family's HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40-2.94, p<0.001). Therefore, homozygous for this complex allele are at risk of having iron overload because they will produce two altered proteins--the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C>G;340+4T>C] has a role, as genetic predisposition factor, on iron overload in the São Miguel population. Independent replication studies in other populations are needed to confirm this association.

Project description:BackgroundThe rearrangements in the 22q11.2 chromosomal region, responsible for the 22q11.2 deletion and microduplication syndromes, are frequently associated with congenital heart disease (CHD). The present work aimed to identify the genetic basis of CHD in 87 patients from the São Miguel Island, Azores, through the detection of copy number variants (CNVs) in the 22q11.2 region. These structural variants were searched using multiplex ligation-dependent probe amplification (MLPA). In patients with CNVs, we additionally performed fluorescent in situ hybridization (FISH) for the assessment of the exact number of 22q11.2 copies among each chromosome, and array comparative genomic hybridization (array-CGH) for the determination of the exact length of CNVs.ResultsWe found that four patients (4.6%; A to D) carried CNVs. Patients A and D, both affected with a ventricular septal defect, carried a de novo 2.5 Mb deletion of the 22q11.2 region, which was probably originated by inter-chromosomal (inter-chromatid) non-allelic homologous recombination (NAHR) events in the regions containing low-copy repeats (LCRs). Patient C, with an atrial septal defect, carried a de novo 2.5 Mb duplication of 22q11.2 region, which could have been probably generated during gametogenesis by NAHR or by unequal crossing-over; additionally, this patient presented a benign 288 Kb duplication, which included the TOP3B gene inherited from her healthy mother. Finally, patient B showed a 3 Mb triplication associated with dysmorphic facial features, cognitive deficit and heart defects, a clinical feature not reported in the only case described so far in the literature. The evaluation of patient B's parents revealed a 2.5 Mb duplication in her father, suggesting a paternal inheritance with an extra copy.ConclusionsThis report allowed the identification of rare deletion and microduplication syndromes in Azorean CHD patients. Moreover, we report the second patient with a 22q11.2 triplication, and we suggest that patients with triplications of chromosome 22q11.2, although they share some characteristic features with the deletion and microduplication syndromes, present a more severe phenotype probably due to the major dosage of implicated genes.

Dataset Information

A comprehensive overview of the cystic fibrosis on the island of Sao Miguel (Azores, Portugal).

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A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal).

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