A5011925993- Genomics and Rare Diseases
- Connective tissue disorders research
- Bone health and treatments
- Bone Metabolism and Diseases
- Acute Lymphoblastic Leukemia research
- Genomic variations and chromosomal abnormalities
- Dermatology and Skin Diseases
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Acute Myeloid Leukemia Research
- Food Allergy and Anaphylaxis Research
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- Allergic Rhinitis and Sensitization
- CRISPR and Genetic Engineering
- Neurogenetic and Muscular Disorders Research
- Dermatological and Skeletal Disorders
- interferon and immune responses
- Cellular transport and secretion
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Genetic and Kidney Cyst Diseases
Karolinska University Hospital
2015-2025
Karolinska Institutet
2016-2025
Science for Life Laboratory
2013-2017
Boğaziçi University
2008-2012
Acıbadem University
2008-2012
Acıbadem Adana Hospital
2012
Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped approximately 5.8 Mb region at 12p13.1 but no candidate gene identified. In international consortium we recruited 19 independent families comprising 107 individuals with pEDS identify the locus, characterize clinical details in those defined genetic causes, try understand...
PURPOSE Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such offers clinically actionable data a prospective broadly inclusive setting remains largely unexplored. METHODS We implemented whole-genome sequencing (WGS) tumor and germline, complemented by whole-transcriptome (RNA-Seq) for all children diagnosed with primary or...
<h3>Background</h3> Point mutations in <i>PDE4D</i> have been recently linked to acrodysostosis, an autosomal dominant disorder with skeletal dysplasia, severe brachydactyly, midfacial hypoplasia and intellectual disability. The purpose of the present study was investigate clinical cellular implications different types gene. <h3>Methods</h3> We studied five acrodysostosis patients three gene dose imbalances involving clinically by whole exome sequencing, Sanger sequencing array comparative...
BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood development. Yet, due variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective study that investigated diagnostic yield clinical impact integrating whole-genome sequencing (gWGS) tumor systematic phenotyping in solid tumors.MethodsgWGS was performed 309 at diagnosis CNS (n =...
ABSTRACT Spondyloocular syndrome is an autosomal-recessive disorder with spinal compression fractures, osteoporosis, and cataract. Mutations in XYLT2, encoding isoform of xylosyltransferase, were recently identified as the cause syndrome. We report on 4 patients, 2 unrelated patients siblings, spondyloocular novel mutations XYLT2. Exome sequencing revealed a homozygous nonsense mutation, NM_022167.3(XYLT2): c.2188C&gt;T, resulting premature stop codon (p.Arg730*) female patient. The...
ABSTRACT Mutations in the PLS3 gene, encoding Plastin 3, were described 2013 as a cause for X-linked primary bone fragility children. The specific role of metabolism remains inadequately understood. Here we describe first time deletions underlying childhood-onset osteoporosis 3 boys from 2 families. We carried out thorough clinical, radiological, and tissue analyses to explore consequences these further elucidate homeostasis. In family 1, affected brothers had deletion exons 4–16 (NM_005032)...
Altogether 95 children with primary bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Two multiple peripheral and spinal fractures low BMD had novel disease-causing PLS3 variants. Children milder phenotypes no pathogenic screening is indicated childhood-onset The study aimed to determine role of children's elucidate associated phenotypic features. cohorts Cohort I comprised 31 patients osteoporosis unknown etiology. II 64 who sustained but...
Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, reported to cause skeletal ciliopathies. Here, we summarize genetic phenotypic 34 affected individuals from 29 families Molecular diagnostic testing was performed using massively parallel sequencing (MPS) combination copy number variant...
Abstract Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions small joints osteolysis leading to joint disruption. Despite its severity, underlying mechanisms are unknown, no susceptibility genes have hitherto been identified. We aimed investigate genetic basis PAM performing massive parallel sequencing in sixty-one patients from Nordic cohort. found rare variants NADPH oxidase 4 ( NOX4 ) four patients. In silico predictions...
The strong association between epidermal barrier gene variants and Atopic Dermatitis (AD) highlights that impaired skin is a key feature in the pathogenesis of AD. Although filaggrin (FLG) major AD risk European Asian populations, disease-associated remain elusive African populations.A previous study has reported tight junction CLDN1 have been associated with susceptibility disease severity African-Americans. Our aim was therefore to investigate Ethiopian population.To how may be involved...
Hundreds of variants associated with atopic dermatitis (AD) and psoriasis, 2 common inflammatory skin disorders, have previously been discovered through genome-wide association studies (GWASs). The majority these are in noncoding regions, their target genes remain largely unclear.We sought to understand the effects on development AD psoriasis by linking them that they regulate.We constructed genomic 3-dimensional maps human keratinocytes during differentiation using targeted chromosome...
The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with broad clinical phenotype due to homozygous missense mutations. ranges from classical presentation in one patient (p.Pro210Leu), severe neurodevelopmental delay brain atrophy...
The skeletal ciliopathies are a heterogeneous group of disorders with significant clinical and genetic variability the main features thoracic hypoplasia short tubular bones. To date, 25 genes have been identified in association ciliopathies. Mutations KIAA0753 gene recently associated Joubert syndrome (JBTS) orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants four patients short-rib type dysplasia. manifestations our variable ranging from fetal lethal to viable moderate...
We have investigated 20 consanguineous families with multiple children affected by rare disorders. Detailed clinical examinations, exome sequencing of as well unaffected family members and further validation likely pathogenic variants were performed. In 16/20 families, we identified in autosomal recessive disease genes (ALMS1, PIGT, FLVCR2, TFG, CYP7B1, ALG14, EXOSC3, MEGF10, ASAH1, WDR62, ASPM, PNPO, ERCC5, KIAA1109, RIPK4, MAN1B1). A number these only rarely been reported previously our...
Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants candidate loci, we screened a cohort of 70 subjects with mild to severe skeletal fragility rare copy-number (CNVs). Our study included 15 primary before age 30 years 55 pathological fracture history normal BMD 16 years. A custom-made...
Abstract Background Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative approximately 85% of cases. In recent years, recessive variants genes involved collagen processing have been found. Hypodontia (< 6 missing permanent teeth) oligodontia (≥ previously reported individuals with OI. The aim the present cross-sectional study was...
Abstract Background De novo variants are a common cause to rare intellectual disability syndromes, associated with low recurrence risk. However, when such occur pre‐zygotically in parental germ cells, the risk might be higher. Still, estimates mainly based on empirical data and prevalence of germline mosaicism is often unknown. Methods To establish parents children syndromes caused by de variants, we performed droplet digital PCR DNA extracted from blood (43 trios), sperm (31 fathers)....
Proliferative vasculopathy and hydranencephaly‐hydrocephaly syndrome ( PVHH , OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder, caused by mutations in FLVCR2 . Hallmarks of the are glomerular central nervous system, severe hydrocephaly, hypokinesia arthrogryphosis. The disorder considered prenatally lethal. We report first patients, brother sister, with survival beyond infancy. patients present phenotype intellectual neurologic disability seizures, absence...