Denise Williams
A5078389378- Prenatal Screening and Diagnostics
- Fetal and Pediatric Neurological Disorders
- Genomic variations and chromosomal abnormalities
- Genetic Syndromes and Imprinting
- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Renal and related cancers
- Cell Adhesion Molecules Research
- Spaceflight effects on biology
- Metabolism and Genetic Disorders
- Probiotics and Fermented Foods
- Tumors and Oncological Cases
- Genomics and Rare Diseases
- Congenital heart defects research
- RNA regulation and disease
- Bacterial Genetics and Biotechnology
- Corneal Surgery and Treatments
- Congenital Ear and Nasal Anomalies
- Biochemical and Molecular Research
- Neonatal and fetal brain pathology
- Ocular Disorders and Treatments
- Parvovirus B19 Infection Studies
- Congenital Anomalies and Fetal Surgery
Birmingham Women’s and Children’s NHS Foundation Trust
2010-2024
Children’s Foundation
2023
Royal College of Obstetricians and Gynaecologists
2021
Cardiff University
2021
University of Siena
2021
Azienda Ospedaliera Universitaria Senese
2021
Birmingham Women's Hospital
1988-2019
St Michael’s Hospital
2019
North Bristol NHS Trust
2019
Imperial College Healthcare NHS Trust
2019
BackgroundFetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; detectable microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy CNVs is routine during the investigation fetal but there little information on clinical usefulness genome-wide next-generation sequencing prenatal setting. We therefore aimed to evaluate proportion fetuses with...
This large prospective cohort study recruited from 34 UK fetal medicine units to evaluate the use of prenatal whole genome sequencing in 610 fetuses with a structural abnormality detected on antenatal ultrasound scanning and no chromosomal abnormality. Overall, diagnostic genetic mutation was identified 8.5% fetuses, more commonly those multisystem anomalies (15.4%), skeletal or cardiac (11.1%). The lowest yield, only 3.2%, isolated increased nuchal translucency first trimester.
The conjugation mechanism of IncP plasmids may be employed to mobilize small non-conjugative from Escherichia coli a wide range different organisms. This strategy has been adapted for use with the Grampositive anaerobe, Clostridium acetobutylicum NCIB 8052. Several shuttle vectors containing replicons pAMβ1 (Enterococcus faecalis), pCB101 (Clostridium butyricum) or pWV01 (Streptococcus cremoris), together cis-acting oriT region RK2, have constructed, and transferred established in this...
NEUROD1 is expressed in both developing and mature beta-cells. Studies mice suggest that this basic helix-loop-helix transcription factor critical the development of endocrine cell lineage. Heterozygous mutations have previously been identified as a rare cause maturity-onset diabetes young (MODY). We aimed to explore potential contribution patients with permanent neonatal diabetes.We sequenced gene 44 unrelated unknown genetic etiology.Two homozygous (c.427_ 428del c.364dupG) were two...
Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (
Development of an accurate and affordable test for the non-invasive prenatal diagnosis Duchenne Becker muscular dystrophies (DMD/BMD) to implement in clinical practice.Cell-free DNA was extracted from maternal blood prepared massively parallel sequencing on Illumina MiSeq by targeted capture enrichment single nucleotide polymorphisms (SNPs) across dystrophin gene chromosome X. Sequencing data were analysed relative haplotype dosage.Seven healthy pregnant donors two DMD carriers all bearing a...
Although technically possible, few clinical laboratories across the world have implemented non-invasive prenatal diagnosis (NIPD) for selected single-gene disorders, mostly owing to elevated costs incurred. Having previously proven that NIPD X-linked disorders can be feasibly in practice, we now developed a test of an autosomal-recessive disorder, spinal muscular atrophy (SMA). Cell-free DNA was extracted from maternal blood and prepared massively parallel sequencing on Illumina MiSeq by...
Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as main cause of syndrome. Here we describe results mutation analysis 62 patients presenting with cataracts myopathy or combinations at least two these. We...
We report molecular genetic analysis of 42 affected individuals referred with a diagnosis aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 and 11 Gillespie syndrome (iris hypoplasia, ataxia mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing two FOXC1. Six deletions plausible cis-regulatory effects identified: five that 3ʹ (telomeric) one...
We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to genetic variations. populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 3), ALMS1 268), and SLC19A2 48) Wolfram type 1, 2, Alström, Thiamine-responsive megaloblastic anemia syndromes, respectively; included 23 previously unpublished novel germline in 17 ALMS1. then investigated...
Most classical aniridia is caused by PAX6 haploinsufficiency. missense variants can be hypomorphic or mimic We hypothesized that also cause previously undescribed disease altering the affinity and/or specificity of genomic interactions. screened in 372 individuals with bilateral microphthalmia, anophthalmia, coloboma (MAC) from Medical Research Council Human Genetics Unit eye malformation cohort (HGUeye) and reviewed data Deciphering Developmental Disorders study. performed cluster analysis...
Introduction In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored experiences professionals involved delivering pES service during first 2 years its delivery NHS. Methods A survey ( n = 159) semi-structured interviews 63) with healthcare professionals, including clinical geneticists,...
<h3>Background</h3> Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, thick skin. Patients often present with a progressive cardiac valvular disease which can lead to early death. In previous study including six GD families, we have mapped the gene on chromosome 9q34.2 identified mutations in <i>A Disintegrin And Metalloproteinase Thrombospondin repeats-like 2</i> (<i>ADAMTSL2</i>). <h3>Methods</h3>...
To assess the visual needs of adult population with Bardet-Biedl syndrome (BBS) and to ensure that this is addressed by a national Service.A cross-sectional analysis all adults under BBS Clinic (Birmingham, United Kingdom) was performed using Ophthalmic Assessment Tool, novel tool designed capture key elements function, impact on lifestyle, clinical findings relevant BBS.Sixty-two patients were confirmed have BBS. mutations identified in 51, most commonly BBS1 (n = 35), BBS2 6), BBS10 5). In...