A5027779716- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Renal and related cancers
- Genetic Neurodegenerative Diseases
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Congenital heart defects research
- Protein Tyrosine Phosphatases
- Reproductive Biology and Fertility
- Birth, Development, and Health
- Kruppel-like factors research
- RNA regulation and disease
- RNA Research and Splicing
- Cleft Lip and Palate Research
- Congenital Ear and Nasal Anomalies
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Growth Hormone and Insulin-like Growth Factors
- Genetic and rare skin diseases.
- Proteoglycans and glycosaminoglycans research
- Ovarian cancer diagnosis and treatment
- Cutaneous Melanoma Detection and Management
- Sperm and Testicular Function
- Tracheal and airway disorders
University College London
2016-2025
William Harvey Research Institute
2023-2025
Queen Mary University of London
2024
Great Ormond Street Hospital
2017-2023
Institute of Child Health
2019
Kobe Pharmaceutical University
2006-2008
University of Toyama
2006
Ishikawa Prefectural Institute for Educational Research and In-Service Training
1997
Kagoshima University
1994
Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, Tp53 have been described individual CMN samples; however, their role the pathogenesis multiple within same subject development features has not clear. We hypothesized that a single postzygotic mutation NRAS could responsible for individual, as well nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples were sequenced after...
Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions are frequently associated with microcephaly and/or epilepsy. Here we report the identification causal mutations Sorting Nexin 14 (SNX14) found seven affected individuals from three unrelated consanguineous families who presented recessively inherited moderate-severe intellectual disability, ataxia, early-onset atrophy, sensorineural hearing loss, distinctive association progressively...
Abstract Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore undertook an exploratory study of transcriptomic landscape clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) matched 46,XX 46,XY control samples between 11 15 weeks post conception ( n = 78). Although most pseudoautosomal region 1 (PAR1) genes are lower monosomy tissues, we also found reduced...
We have demonstrated a defect in expression of chondroitin 4-O-sulfotransferase-1 (C4ST-1) murine sog9 cells, which are poorly sensitive to infection by herpes simplex virus type 1 (HSV-1). Sog9 cells were previously isolated as CS-deficient from gro2C partially resistant HSV-1 and defective the heparan sulfate (HS) because splice site mutation EXT1 gene encoding HS-synthesizing enzyme. Here we detected small amount CS chains with drastic decrease 4-O-sulfation compared parental cells....
Wnt-3a is a ligand that activates the beta-catenin-dependent pathway in Wnt signaling, which implicated numerous physiological events such as morphogenesis. So far, heparan sulfate (HS) proteoglycans have been highlighted low affinity receptor for morphogens containing Wnts. Here we show importance of chondroitin (CS) efficient signaling and structural features CS required regulation signaling. was depressed mouse L cell mutant, called sog9, defective EXT1 gene encoding HS-synthesizing...
Abstract Context Small for gestational age (SGA) can be the result of fetal growth restriction, which is associated with perinatal morbidity and mortality. Mechanisms that control prenatal are poorly understood. Objective The aim current study was to gain more insight into failure determine an effective diagnostic approach in SGA newborns. We hypothesized one or copy number variations (CNVs) disturbed methylation sequence variants may present genes growth. Design A prospective cohort...
Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed hormone that critical for in utero mice. Its role human fetal has remained ambiguous, as it only been studied term tissues. Conversely the maternally suppressor, PHLDA2, significant negative correlation between its placental expression and birth weight.The aim of this study to address early gestation IGF1, IGF2, their receptors IGF1R IGF2R, PHLDA2 on weight.Real-time quantitative PCR was used...
Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical psychosocial sequelae. Approximately 10% POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development function. Recently, Ythdc2, an RNA helicase N6-methyladenosine reader, emerged as regulator meiosis mice. Here, we describe homozygous pathogenic variants YTHDC2 3 early-onset from 2 families: c. 2567C>G, p.P856R the...
Abstract Context Establishing the genetic basis of early-onset primary ovarian insufficiency (EO-POI, <25 years) is important, but defining variant pathogenicity challenging. Objective To elucidate architecture EO-POI in a unique, large cohort. Setting Young women with (n=149; n=31 familial, n=118 sporadic) attending specialist reproductive unit. Design Exome sequencing was performed. After filtering, variants were retained which 1) rare/novel (minor allele frequency <0.01%);...
<title>Abstract</title> <bold>Introduction</bold>: Monoallelic dominant negative <italic>LZTR1</italic> gene variants have been implicated as a cause of NS due to hyperactivation the canonical RAS-MAPK signalling pathway. Missense <italic>LZTR1 </italic>variants associated with defective ubiquitination theoretically leading increased Ras substrate availability and altered p53 signalling. We investigated role LZTR1 in this <bold>Methods</bold>: Single nucleotide substitutions were created by...
Birth weight is an important indicator of both perinatal and adult health, but little known about the genetic factors contributing to its variability. Intrauterine growth restriction a leading cause morbidity mortality also associated with disease. A significant correlation has been reported between lower birth increased expression maternal PHLDA2 allele in term placenta (the normal imprinting pattern was maintained). However, mechanism that explains transcriptional regulation on utero yet...
Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among most common birth worldwide. This study focuses on anencephaly, which despite having a similar frequency spina bifida and being type of NTD observed in mouse models, has had more limited inclusion genetic studies. A influence is strongly implicated determining risk molecular diagnosis...
Background Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature may be ameliorated by treatment. Approximately 50% of patients have loss methylation the control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%–10% maternal uniparental disomy chromosome 7. Most published research focuses childhood phenotype. Our aim was to describe phenotypic characteristics older with SRS. Methods A retrospective cohort 33 individuals a confirmed molecular...
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate complexities etiology this heterogeneous condition, factor remains incompletely understood. Here, we describe mutations in HYAL2 gene as a cause syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, critical component developing heart palatal shelf matrix. Transfection assays...
<ns3:p><ns3:bold>Background:</ns3:bold> Cyclin-dependent kinase inhibitor 1C (CDKN1C) is a key negative regulator of cell growth encoded by paternally imprinted/maternally expressed gene in humans. Loss-of-function variants <ns3:italic>CDKN1C</ns3:italic> are associated with an overgrowth condition (Beckwith-Wiedemann Syndrome) whereas “gain-of-function” <ns3:italic>CDKN1C </ns3:italic>that increase protein stability cause restriction as part IMAGe syndrome...
Diabetes mellitus (DM) risk factors in Turner Syndrome (TS) may include autoimmunity, obesity, beta-cell dysfunction, genetic predisposition and insulin resistance (IR).
Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. The range additional clinical associations is expanding includes disrupted placental development, poor post-natal growth endocrine features. Increasingly, milder phenotypic features such as hypospadias small for gestational age (SGA) boys normal adrenal function are reported. Some...
Abstract Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) both humans and dogs. Studies implicating phenotypic consequences of mutations to be subcellular disruption autophagy lipid metabolism have been limited vitro investigation patient-derived dermal fibroblasts, laboratory engineered cell lines developmental analysis zebrafish morphants. homologues Snz ( Drosophila ) Mdm1 (yeast) also conducted, demonstrated an important biochemical role during...
Women with Turner syndrome (TS) (45,X and related karyotypes) have an increased prevalence of conditions such as diabetes mellitus, obesity, hypothyroidism, autoimmunity, hypertension, congenital cardiovascular anomalies (CCA). Whilst the risk developing these co-morbidities may be partly to haploinsufficiency key genes on X chromosome, other mechanisms involved. Improving our understanding underlying processes is important develop personalized approaches management.