A5056326576- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Prenatal Screening and Diagnostics
- Lysosomal Storage Disorders Research
- Genomic variations and chromosomal abnormalities
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Diet and metabolism studies
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Genomics and Rare Diseases
- Congenital Anomalies and Fetal Surgery
- Neonatal Health and Biochemistry
- Genetic Syndromes and Imprinting
- RNA Research and Splicing
- Retinal Development and Disorders
- Congenital heart defects research
- Fetal and Pediatric Neurological Disorders
- Cleft Lip and Palate Research
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Oral and Maxillofacial Pathology
- Williams Syndrome Research
- Corneal Surgery and Treatments
Tartu University Hospital
2009-2023
University of Tartu
2002-2023
To delineate phenotypic heterogeneity, we describe the clinical features of a cohort patients with GABRA1 gene mutations.Patients mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data collected. Functional analysis 4 selected was performed using Xenopus laevis oocyte expression system.The study included 16 novel probands 3 additional family members disease-causing mutation in gene. The spectrum varied from unspecified epilepsy (1), juvenile...
Abstract KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context European collaborative study, we collected largest cohort KBGS patients (49). A combined array- based Comparative Genomic Hybridization next generation sequencing (NGS) approach investigated both genomic Copy...
Vitamin B12 deficiency seems to be more common worldwide than previously thought. However, only a few reports based on data from newborn screening (NBS) programs have drawn attention that subject. In Estonia, over the past three years, we diagnosed 14 newborns with congenital acquired vitamin deficiency. Therefore, incidence of condition is 33.8/100,000 live births, which considerably believed. None had any clinical symptoms associated before treatment, and all biochemical markers normalized...
The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two isoforms, Stx5 Long (Stx5L) from first starting methionine and Short (Stx5S) an alternative at position 55. this study, we identify a human disorder caused by single missense substitution in second (p.M55V), resulting complete loss of short isoform. Patients suffer early fatal multisystem disease, including severe liver...
Accurate diagnosis for patients living with neurodevelopmental disorders is often met numerous challenges, related to the ambiguity of findings and lack specificity in genetic variants leading pathology. Genome-wide DNA methylation analysis has been used develop highly sensitive specific 'episignatures' as biomarkers capable differentiating classifying complex disorders. In this study we describe distinct episignatures KAT6A syndrome, caused by pathogenic lysine acetyltransferase A gene...
Abstract Background Multiple acyl‐CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II, is a mitochondrial fatty acid oxidation disorder caused by variants in ETFA , ETFB, and ETFDH . Recently, riboflavin transporter genes the FAD gene have been associated with MADD‐like phenotype. Methods We present case of MADD identified newborn biochemical screening full‐term infant suggestive both medium‐chain MADD. Urine organic GC/MS analysis was concerning for disorders....
Silver-Russell syndrome (SRS) and Beckwith-Wiedemann (BWS) are 2 opposite growth-affecting disorders. The common molecular cause for both syndromes is an abnormal regulation of genes in chromosomal region 11p15, where imprinting control regions (ICR) fetal postnatal growth. Also, many submicroscopic disturbances like duplications 11p15 have been described among SRS BWS patients. Duplications involving ICRs or BWS, depending on which parent the aberration inherited from. We describe to our...
Abstract Inherited metabolic disorders (IMD) are a group of hereditary diseases wherein the impairment biochemical pathway is intrinsic to pathophysiology disease. Estonia's small population and nationwide digitalised healthcare system make it possible perform an epidemiological study that covers whole population. A was performed in Tartu University Hospital, which only tertiary care unit Estonia for diagnosing patients with IMD, define prevalence live birth IMDs effectiveness new diagnostic...
To study the frequency of methylation abnormalities among Estonian patients selected according to published clinical diagnostic scoring systems for Silver-Russell syndrome (SRS) and Beckwith-Wiedemann (BWS).Forty-eight with suspicion SRS (n = 20) or BWS 28) were included in group, whom methylation-specific multiplex ligation-dependant probe amplification analysis 11p15 region was made. In addition, minimal score either BWS, multilocus single nucleotide primer extension assay performed.Five...
Background: Rare diseases are an important population health issue and many promising therapies have been developed in recent years. In light of novel genetic treatments expected to significantly improve spinal muscular atrophy (SMA) patients' quality life the urgent need for SMA newborn screening (NBS), new epidemiological data were needed implement NBS Estonia. Objective: We aimed describe birth prevalence years 1996-2020 compare results with previously published data. Methods:...
Abstract Background Pathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic phenotypic information. Methods Data were collected via a structured questionnaire. Sequencing was performed these patients mostly due diagnostic purpose. A little more than half variant carriers identified by NGS; other six family members. Results Here, report 13 individuals heterozygous...
Holt-Oram syndrome (HOS) is an autosomal dominant developmental defect involving preaxial radial ray upper limb deformity and variable cardiac defects. It has been demonstrated that HOS caused by mutations in the T-box transcription factor gene <i>TBX5</i>. Numerous germline (more than 60) of this produce preterminal stop codons, which lead to synthesis a truncated nonfunctional TBX5 protein. The haplo-insufficiency <i>TBX5</i> most significant cause HOS. We report on...
The present study provides a retrospective overview of the cohort phenylketonuria (PKU) patients in Estonia. Based on available data, clearly cluster into two distinct groups: with late diagnosis and start therapy (N = 46), who were born before 1993 when national newborn screening programme was launched, screened babies 48) getting their diagnoses at least couple weeks after birth.Altogether 153 independent phenylalanine hydroxylase (PAH) alleles from 92 analysed study, wherein 80% them...
Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WBP4 (WW Domain Binding Protein 4) is part of the early spliceosomal complex, and was not described before context pathologies. Ascertained through GeneMatcher we identified eleven patients from eight families, with a severe neurodevelopmental syndrome variable manifestations. Clinical manifestations included hypotonia, global developmental delay, intellectual disability, brain...
Blood phenylalanine (Phe) values from the dried blood spots of all Estonian phenylketonuria (PKU) patients have been deposited into a unified electronic laboratory database for eight years, providing an opportunity to assess adherence dietary recommendations over time and observe patient practices both individually collectively. Our results demonstrate generally good clinical during first six years life, as percentage with median Phe fitting under national recommendation levels were 95%, 84%...
Introduction of cell-free fetal DNA (cff-DNA) testing in maternal blood opened possibilities to improve the performance combined first-trimester screening (cFTS) terms better detection trisomies and lowering invasive rate. The use new molecular methods, such as chromosomal microarray analysis (CMA) next-generation sequencing (NGS), has shown benefits prenatal diagnosis genetic diseases, which are not detectable with cff-DNA screening, but require an procedure.The objective this study was...
Kaasasundinud sudamerike (KSSR) on uks levinum kaasasundinud arengurike, mille tekkes oluline roll geneetilistel teguritel. Parilikud KSSRid jaotatakse sundroomseteks ja mittesundroomseteks. Pohjused voivad olla nii kromosomaalsed (nt Downi sundroom, Williamsi sundroom), uhe geeni haired Allagille’i sundroom) kui ka mitmetegurilised (parilik eelsoodumus). Diagnostikaks voimalik kasutada tsutogeneetilist uuringut, FISH-analuusi, molekulaarseid teste geenimutatsioonide tuvastamiseks ning...