A5080345669- Congenital heart defects research
- Congenital Heart Disease Studies
- Renal and related cancers
- Pluripotent Stem Cells Research
- Genetic Syndromes and Imprinting
- Pancreatic function and diabetes
- Mesenchymal stem cell research
- Neonatal Respiratory Health Research
- Genetic and Kidney Cyst Diseases
- RNA modifications and cancer
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Tracheal and airway disorders
- Genetics and Neurodevelopmental Disorders
- Sexual Differentiation and Disorders
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- Osteoarthritis Treatment and Mechanisms
- Bone fractures and treatments
- Coronary Artery Anomalies
- CRISPR and Genetic Engineering
- Birth, Development, and Health
- RNA Research and Splicing
- Congenital Ear and Nasal Anomalies
- Genomic variations and chromosomal abnormalities
- Asthma and respiratory diseases
Universidade Federal de São Paulo
2016-2024
University of Southampton
2010-2022
The University of Melbourne
2020
Cairns Hospital
2014-2020
Ulster Hospital
2019
Cleveland Clinic
2018
Center for Life Sciences
2016
University of Illinois System
2016
Southampton General Hospital
2002-2015
University Hospital Southampton NHS Foundation Trust
2001-2015
We present clinical data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22q11. Twenty-eight percent cases where parents had been tested inherited deletions, a marked excess maternally (maternal 61, paternal 18). Eight died, over half these month birth and majority 6 months. All but one deaths were result congenital heart disease. Clinically significant immunological problems very uncommon. Nine cleft palate 32% velopharyngeal insufficiency, 60%...
DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22q11. We report clinical findings 44 cases. propose that should be seen as severe end spectrum embraced by acronym CATCH 22 syndrome; Cardiac defects, Abnormal facies, Thymic Cleft palate, Hypocalcaemia resulting 22q11 deletions.
Understanding gene expression profiles during early human pancreas development is limited by comparison to studies in rodents. In this study, from the inception of pancreatic formation, embryonic epithelial cells, approximately half which were proliferative, expressed nuclear PDX1 and cytoplasmic CK19. Later, fetal pancreas, insulin was most abundant hormone detected first trimester largely non-proliferative cells. At sequential stages development, as number insulin-positive cell clusters...
The conotruncal anomaly face syndrome was described in a Japanese publication 1976 and comprises dysmorphic facial appearance outflow tract defects of the heart. authors subsequently noted similarities to Shprintzen DiGeorge syndrome. Chromosome analysis five cases did not show deletion at high resolution, but fluorescent situ hybridisation using probe DO832 showed within chromosome 22q11 all cases.
Alström syndrome is a rare autosomal recessive disorder caused by mutations in novel gene of unknown function, ALMS1. Central features include obesity, insulin resistance, and type 2 diabetes, therefore investigating ALMS1 function stands to offer new insights into the pathogenesis these common conditions. To begin this process, we have analyzed subcellular localization tissue distribution immunofluorescence. We show that widely expressed localizes centrosomes base cilia. Fibroblasts with...
The velo-cardio-facial syndrome (VCFS) and DiGeorge sequence (DGS) have many similar phenotypic characteristics, suggesting that in some cases they share a common cause. DGS is known to be associated with monosomy for region of chromosome 22q11, DNA probes been shown detect these deletions even patients apparently normal chromosomes. Twelve VCFS were examined 22q11 was found all patients. used this study could not distinguish the locus locus, indicating genes involved haploinsufficiencies...
Congenital heart defects (CHDs) are the most common birth defect worldwide and a leading cause of neonatal mortality. Nonsyndromic atrioventricular septal (AVSDs) an important subtype CHDs for which genetic architecture is poorly understood. We performed exome sequencing in 13 parent-offspring trios 112 unrelated individuals with nonsyndromic AVSDs identified five rare missense variants (two arose de novo) highly conserved gene NR2F2, very significant enrichment (p = 7.7 × 10−7) compared to...
Alström syndrome is a monogenic recessive disorder featuring an array of clinical manifestations, with systemic fibrosis and multiple organ involvement, including retinal degeneration, hearing loss, childhood obesity, diabetes mellitus, dilated cardiomyopathy (DCM), urological dysfunction, pulmonary, hepatic, renal failure. We evaluated large cohort patients for mutations in the ALMS1 gene. In total, 79 disease-causing variants were identified, which 55 are novel mutations. The primarily...
Cytochrome P450 17alpha-hydroxylase/17-20 lyase (P450(C17)) is a critical branchpoint enzyme for steroid hormone biosynthesis. During human gestation, P450(C17) required the production of dehydroepiandrostenedione sulfate by fetal adrenal cortex and testicular androgens that mediate male sexual differentiation. In this study, we investigate regulation CYP17 gene two orphan nuclear receptors, steroidogenic factor 1 (SF-1) DAX1. embryos, SF-1 DAX1 are expressed throughout developing from its...
A wide spectrum of birth defects are caused by deletions the DIGeorge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such have now been examined and a minimally deleted 300kb defined. Within these sequences we Identified gene expressed during murine embryogenesIs. The gene, named TUPLE1, Its homologue, encodes protein containing repeated motifs similar to WD40 domains found In beta-transducIn/enhancer split (TLE) family. TUPLE1 product has several features...
Based on evidence suggesting similarities to human embryonic stem cells, germ (hEG) cells have been advocated as an alternative pluripotent cell resource but so far received limited attention. To redress this imbalance, fetal gonads were collected for the isolation and culture of primordial at 7-9 weeks postconception. We provide derivation, culture, differentiation hEG in vitro. This includes expression markers characteristic retention normal XX or XY karyotypes, demonstration pluripotency,...
There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported.We recruited healthy, prepubertal at term singleton pregnancy. The study group were conceived using IVF with fresh embryo transfer, whereas controls naturally conceived. Anthropometric measurements, bone age, dual-energy x-ray absorptiometry, fasting serum glucose, insulin,...
NANOG, POU5F1, and SOX2 are required by the inner cell mass of blastocyst act cooperatively to maintain pluripotency in both mouse human embryonic stem cells. Inadequacy any one them causes loss undifferentiated state. Mouse primordial germ cells (PGCs), from which pluripotent (EGCs) derived, also express SOX2. Thus, a similar expression profile has been predicted for PGCs. Here we show RT-PCR, immunoblotting, immunohistochemistry that PGCs POU5F1 NANOG but not SOX2, with no evidence...
Appropriate temporospatial expression of the transcription factor SOX9 is important for normal development a wide range organs. Here, we show that when expressed ectopically, target genes become are associated with disease. Histone deacetylase inhibitors in clinical trials cancer therapy induced via enhanced recruitment nuclear Y (NF-Y) to CCAAT elements proximal promoter. The effect histone could be elicited cells normally lack SOX9, such as hepatocytes. In human fetal hepatocytes, this...