A5049916521- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Sexual Differentiation and Disorders
- Prenatal Screening and Diagnostics
- Renal and related cancers
- Forensic and Genetic Research
- Hearing, Cochlea, Tinnitus, Genetics
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Genetic Syndromes and Imprinting
- Chromosomal and Genetic Variations
- Genetic diversity and population structure
- Cystic Fibrosis Research Advances
- Vestibular and auditory disorders
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- Immunodeficiency and Autoimmune Disorders
- Nuclear Structure and Function
- Neonatal Respiratory Health Research
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Race, Genetics, and Society
- Hemophilia Treatment and Research
Universidade do Porto
2015-2025
Cincinnati Children's Hospital Medical Center
2025
University of Cincinnati
2025
Universidade Federal de São Paulo
2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015-2023
Hospital de São João
2015-2023
Hospital Pedro Hispano
2016
Centro Hospitalar do Porto
2014
University of Minho
2014
University of Aveiro
2014
Genomic imprinting marks in the male germ line are already established adult germinal stem cell population. We studied methylation patterns of H19 and MEST imprinted genes sperm control oligozoospermic patients, by bisulphite genomic sequencing. here report that 7 out 15 (46.7%) patients with a count below 10 × 106/ml display defective and/or genes. In these cases, hypomethylation was observed 5.54% (1.2–8.3%) complete unmethylation 2.95% (0–5.9%) clones. Similarly, for CTCF-binding site 6,...
Abstract De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de an important severe male infertility and explain portion of the genetic causes this understudied disorder. To test hypothesis, we utilize trio-based exome sequencing cohort 185 infertile males their unaffected parents. Following systematic analysis, 29 145 rare (MAF < 0.1%) protein-altering classified as possibly causative phenotype. observed significant...
Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in human population. We hypothesized men spermatogenic impairment, a disease unknown genetic architecture common cause male infertility, are enriched for rare deleterious compared to normal spermatogenesis. After assaying genomewide SNPs CNVs 323 Caucasian idiopathic impairment more than 1,100 controls, we estimate each autosomal deletion detected...
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder the lung defined by constellation characteristic histopathological features. Nonpulmonary anomalies involving organs gastrointestinal, cardiovascular, genitourinary systems have been identified in approximately 80% patients ACD/MPV. We collected DNA pathological samples from more than 90 infants ACD/MPV their family members. Since publication our initial report four point...
Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining genetic basis NOA has proven challenging, advanced classification subforms not based on genetics, but simple description testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed cases identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes 2-stage burden test with 2072 11,587 fertile controls. The disrupted are...
We have developed a rapid screening protocol for deletion analysis of the complete AZFa sequence (i.e. 792 kb) on Y chromosome patients with idiopathic Sertoli-cell-only (SCO) syndrome. This was mapped earlier in proximal Yq11 and first found SCO patient JOLAR, now designated as reference patient. show that similar deletions occur frequency 9% group. In two multiplex polymerase chain reaction experiments, were identified by typical pattern four new sequence-tagged sites (STS): AZFa-prox1,...
Deletions of the DAZ gene family in distal Yq11 are always associated with deletions azoospermia factor c (AZFc) region, which we now estimate extends to 4.94 Mb. Because more Y families located this chromosomal and expressed like only male germ line, testicular pathology complete AZFc cannot predict functional contribution human spermatogenesis. We therefore established a copy specific deletion analysis based on DAZ-BAC sequences GenBank. It includes eight DAZ-DNA PCR markers [six...
The aim of the present work was to outcomes patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection (ICSI), either using fresh (TESE) or frozen-thawed (TESE-C) testicular and ejaculated (EJAC). originality this resides in comparisons between different types Y-microdeletions (AZFa, AZFb, AZFc) treatments, detailed demographic, stimulation, embryological, clinical, newborn (NB) outcomes. Of 125 Y-microdeletions, 33 presented severe oligozoospermia (18 performed...
ObjectiveTo characterize the deletion patterns and its breakpoints in oligozoospermic patients presenting AZFb AZFc microdeletions to understand recombination mechanisms underlying these microdeletions.DesignCase report.SettingGenetics Department of Faculty Medicine Porto, Portugal.Patient(s)Two men with severe oligozoospermia two nonobstructive azoospermia identified as having different AZFb+c via Y chromosome microdeletion analysis.Intervention(s)Definition fine characterization respective...
Genomic imprinting is defined as an epigenetic modification that leads to parent-of-origin specific monoallelic expression. Some current research on the fetal control growth has been focused study of genes display imprinted expression in utero. Four genes, two paternally expressed (IGF2 and PEG10) maternally (PHLDA2 CDKN1C), are well known play a role placental development. Pregnancy loss general reproductive population very common occurrence other genetic causes beyond chromosomal...
The introduction of the benchtop massive parallel sequencers made it possible for majority clinical diagnostic laboratories to gain access this fast evolving technology. In study, using Ion Torrent Personal Genome Machine, we present a strategy molecular diagnosis hereditary breast and ovarian cancer respective analytical validation. methodology relies on multiplex PCR amplification BRCA1 BRCA2 genes combined with variant prioritization pipeline, designed minimize number false-positive calls...
Deletions of the AZFc region in Yq11.2, which include DAZ gene family, are responsible for most cases male infertility and were associated with severe oligozoospermia also a variable testicular pathology. To uncover functional contribution to human spermatogenesis, copy-specific deletion analysis was previously established showed that DAZ1/DAZ2 deletions associate oligozoospermia. In this study we applied same screening method 50 control fertile males 91 non-obstructive azoospermic males, 39...
BACKGROUND: Cystic fibrosis conductance transmembrane regulator (CFTR) gene mutations and IVS8 poly(T) variants in Portuguese patients with bilateral (CBAVD) unilateral (CUAVD) congenital absence of the vas deferens remain to be evaluated. METHODS: Patient screening was carried out by PCR, denaturing gradient gel electrophoresis DNA sequencing. RESULTS: CFTR were found 18 31 (58.1%) CBAVD three four (75%) CUAVD patients. The most frequent F508del R334W G542X CUAVD, allelic frequencies (6.5%)...
A de novo reciprocal translocation 46,X,t(Y;1)(q12;q12) was found in an azoospermic male with meiotic arrest. Cytogenetics and fluorescent situ hybridization (FISH) were used to define the karyotype, breakpoints homologue pairing. SRY (Yp), Yq11.2-AZF regions, DAZ gene copies distal Yq12 heterochromatin studied by PCR restriction analysis using sequence-tagged sites single nucleotide variants. High resolution GTL, CBL DA-DAPI staining revealed a (Y;1) all metaphases normal karyotype...
Microdeletions in AZFa, AZFb and AZFc regions lead to different patterns of male infertility, from severe oligozoospermia non-obstructive azoospermia. Intrachromosomal homologous recombination mechanisms were already identified patients with simultaneous microdeletions the regions. Ten atypical deletion studied. The definition those fine characterization respective breakpoints performed using sequence tagged sites/single nucleotide variants-PCR DNA sequencing. Y-chromosome haplogroups...
What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) patients with non-obstructive azoospermia (NOA)?One 28 NOA cases carried an identifiable, medically actionable SF.In addition to molecular diagnostics, ES allows assessment clinically disease-related gene variants that are not connected patient's primary diagnosis, but knowledge which may allow prevention, delay or amelioration late-onset monogenic conditions. Data on SFs...
The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates is known play an essential role in gonadal development maintenance of spermatogenesis mice. In humans, the genomic region harboring DMRT cluster implicated disorders recently DMRT1 deletions were shown be associated with non-obstructive azoospermia (NOA). this work, we have employed different methods screen a cohort Portuguese NOA patients for exonic...