Cristina Dias
A5013994823- Genomic variations and chromosomal abnormalities
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Neurogenetic and Muscular Disorders Research
- Hereditary Neurological Disorders
- Neurological diseases and metabolism
- Dermatological and Skeletal Disorders
- Congenital Ear and Nasal Anomalies
- Genetic Neurodegenerative Diseases
- Chromosomal and Genetic Variations
- Porphyrin Metabolism and Disorders
- Genomics and Rare Diseases
- Muscle Physiology and Disorders
- Metabolism and Genetic Disorders
- Cutaneous Melanoma Detection and Management
- AI in cancer detection
- Connective tissue disorders research
- Epigenetics and DNA Methylation
- Lipid metabolism and biosynthesis
- Cleft Lip and Palate Research
- Genetic Associations and Epidemiology
- Hedgehog Signaling Pathway Studies
Guy's and St Thomas' NHS Foundation Trust
2024
Great Ormond Street Hospital
2024
King's College London
2018-2024
The Francis Crick Institute
2017-2024
University College London
2024
St Thomas' Hospital
2021
Great Ormond Street Hospital for Children NHS Foundation Trust
2020-2021
Pediatrics and Genetics
2019
University of British Columbia
2008-2018
Wellcome Sanger Institute
2013-2017
Mutations in the gene encoding phospholipase A(2) group VI (PLA2G6) are associated with two childhood neurologic disorders: infantile neuroaxonal dystrophy (INAD) and idiopathic neurodegeneration brain iron accumulation (NBIA). INAD is a severe progressive psychomotor disorder which axonal spheroids found brain, spinal cord, peripheral nerves. High globus pallidus an inconsistent feature of INAD; however, it diagnostic criterion NBIA, describes clinically genetically heterogeneous disorders...
Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number genes implicated in ID, but their roles neurodevelopment remain largely unexplored. Here we report ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations <i>BCL11A,</i> encoding transcription factor that putative member the BAF swi/snf chromatin-remodeling complex. Using comprehensive...
Autosomal dominant cutis laxa (ADCL) is characterized by a typical facial appearance and generalized loose skin folds, occasionally associated with aortic root dilatation emphysema. We sequenced exons 28–34 of the ELN gene in five probands ADCL features found de novo heterozygous mutations: c.2296_2299dupGCAG (CL-1), c.2333delC (CL-2), c.2137delG (CL-3), c.2262delA (monozygotic twin CL-4 CL-5), c.2124del25 (CL-6). Four (CL-1,-2,-3,-6) presented progressive dilatation. CL-2 CL-3 also had...
Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA activate gene expression, though mechanisms through which pioneer remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that endogenous expression of neurogenic factor ASCL1, considered a classical factor, defines transient population progenitors human neural differentiation. Testing ASCL1's function knockout model define the unbound state, found...
Abstract An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge manifestations mutational spectrum is lacking. To address this, we performed detailed analysis 42 -related IDD (BCL11A-IDD, a.k.a. Dias-Logan syndrome) ascertained through an international collaborative network, reviewed 35 additional previously reported patients. Analysis 77 affected identified 60 unique disease-causing (30...
Significance The growing size and sophistication of genome-wide association studies have led to the identification variants which are clearly reliably associated with obesity. A strong between increased BMI a region human chromosome 2, near gene TMEM18 , has been repeatedly demonstrated in children adults. function control appetitive behavior body composition poorly characterized. In murine models, we show germline loss results weight gain while adult onset hypothalamic overexpression loss,...
The most important factor that complicates the work of dysmorphologists is significant phenotypic variability human face. Next-Generation Phenotyping (NGP) tools assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted patients from populations different their training data. To end, we systematically analyzed impact genetic ancestry on facial dysmorphism. For purpose, established GestaltMatcher Database (GMDB) as a reference dataset for...
Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria classified as type I (silent heterozygotes) non-type (heterozygotes with urinary hyperexcretion cystine). Molecularly, A (mutations on SLC3A1 gene) B SLC7A9 gene). The goal this study to provide comprehensive clinical, biochemical molecular characterization cohort 12 Portuguese patients affected order insight into...
Cleavage and polyadenylation of mRNAs is essential for transcription termination gene expression, yet variants disrupting conserved sequences to this process are often overlooked as putative causal in individuals with rare Mendelian disorders. Using deep learning models, we identified enrichment ultrarare alleles predicted disrupt a large cohort undiagnosed probands disease disorders from the Genomics England 100kGP dataset. These predominantly located 3′ UTRs genes where protein-coding have...
Abstract Theobromine, a commonly consumed dietary alkaloid derived from cocoa, has been linked to extended lifespan in model organisms and health benefits humans. We examined associations between circulating theobromine intake, measured using serum metabolomics, blood-based epigenetic markers of biological ageing two European human population-based cohorts. Serum levels were significantly associated with reduced age acceleration, as by GrimAge (p<2e-7) DNAmTL (p<0.001) over 500...
In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified previously reported homozygous mutation in the CAPN3 gene an individual with undiagnosed limb girdle muscular dystrophy, evaluated generalizable clinical tool by assessing targeting efficiency and coverage of 88 genes associated muscle disease (MD) spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting...
Hereditary spastic paraplegias and related genetically heterogeneous disorders may be difficult to distinguish clinically. The FA2H gene has been associated with autosomal recessive neurodegenerative phenotypes encompassing paraplegia or without dystonia, demyelinating leukodystrophy. To date, few individuals mutations in the have described. We report a 5-year-old girl of mixed Filipino Vietnamese origin who presented progressive lower limb spasticity periventricular leukomalacia. clinical...
The establishment of Locus Specific Databases (LSDB) is a crucial aspect for the Human Genetics field and one aims Variation Project. We report development publicly accessible LSDB NIPBL gene (http://www.lovd.nl/NIPBL) implicated in Cornelia de Lange Syndrome (CdLS). This rare disorder characterized by developmental growth retardation, typical facial features, limb anomalies, multiple organ involvement. Mutations gene, product which involved control cohesion complex, account over half...
Focal dermal hypoplasia (FDH, Goltz syndrome), is an X-linked dominant mesoectodermal developmental disorder, involving skin, skeleton, eyes, teeth, and other organs. Mutations in PORCN, which stimulates the secretion of wingless family signal proteins, are found FDH patients. A female fetus presented at 34 weeks gestation with interuterine growth restriction (IUGR), asymmetry, limb anomalies, microphthalmia, lung anomaly. was confirmed birth, hypoplastic areas malformation limbs,...
<title>Abstract</title> The most important factor that complicates the work of dysmorphologists is significant phenotypic variability human face. Next-Generation Phenotyping (NGP) tools assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted patients from populations different their training data. To end, we systematically analyzed impact genetic ancestry on facial dysmorphism. For purpose, established GestaltMatcher Database (GMDB) as...
The spondylo-meta-epiphyseal dysplasias are an expanding group of skeletal with specific features differentiating each subtype. We review the precocious carpal mineralization, unique metacarpal shape, triangular distal phalanges and mushroom cloud-shaped proximal present at early age in dysplasia, short limb-abnormal calcification type (SMED SL-AC) report two patients clinical radiographic consistent SMED SL-AC, who died suddenly because spinal cord compression. presented female siblings,...
Abstract Purpose Heterozygous variants in BCL11A underlie an intellectual developmental disorder with persistence of fetal hemoglobin (BCL11A-IDD, a.k.a. Dias-Logan syndrome). We sought to delineate the genotypic and phenotypic spectrum BCL11A-IDD. Methods performed in-depth analysis 42 patients BCL11A-IDD ascertained through a collaborative network clinical research colleagues. also reviewed 33 additional affected individuals previously reported literature or available public repositories...