Publications by authors named "Eve Vaidla"

5 Publications

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A prenatally diagnosed case of Meckel-Gruber syndrome with novel compound heterozygous pathogenic variants in the TXNDC15 gene.

Mol Genet Genomic Med 2019 05 9;7(5):e614. Epub 2019 Mar 9.

Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.

Background: Meckel-Gruber syndrome (MKS) is a well-known rare disease that can be detected on prenatal ultrasound. Meckel-Gruber syndrome has very heterogeneous etiology; at least, 17 genes have been described in association with MKS. The characteristic findings in fetuses affected by MKS are encephalocele (usually occipital), postaxial polydactyly, and polycystic dysplastic kidneys. However, the association of the TXNDC15 gene with MKS has been reported only once before in three consanguineous families.

Methods: We report a new case of MKS diagnosed at 12 + 1 weeks of gestation with typical ultrasound findings, but with novel compound heterozygous pathogenic variants in the TXNDC15 gene identified by whole-exome sequencing (WES).

Results: This is the second clinical report supporting TXNDC15 as a novel causative gene of MKS, and the first describing a case in a non-consanguineous family with causative compound heterozygous mutations.

Conclusions: Meckel-Gruber syndrome is a very heterogeneous syndrome in terms of the associated causal genes. In the first-line diagnosis, we used an next-generation sequencing (NGS)-based large gene panel, but only 10 MKS genes were available on the platform used. In the case of prenatal ultrasound findings that are highly suggestive of MKS and a negative NGS MKS gene panel, WES should also be performed to not miss rare gene associations.
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http://dx.doi.org/10.1002/mgg3.614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503012PMC
May 2019

Chromosomal microarray analysis as a first-tier clinical diagnostic test: Estonian experience.

Mol Genet Genomic Med 2014 Mar 9;2(2):166-75. Epub 2014 Jan 9.

Department of Genetics, United Laboratories, Tartu University Hospital Tartu, Estonia ; Department of Pediatrics, University of Tartu Tartu, Estonia.

Chromosomal microarray analysis (CMA) is now established as the first-tier cytogenetic diagnostic test for fast and accurate detection of chromosomal abnormalities in patients with developmental delay/intellectual disability (DD/ID), multiple congenital anomalies (MCA), and autism spectrum disorders (ASD). We present our experience with using CMA for postnatal and prenatal diagnosis in Estonian patients during 2009-2012. Since 2011, CMA is on the official service list of the Estonian Health Insurance Fund and is performed as the first-tier cytogenetic test for patients with DD/ID, MCA or ASD. A total of 1191 patients were analyzed, including postnatal (1072 [90%] patients and 59 [5%] family members) and prenatal referrals (60 [5%] fetuses). Abnormal results were reported in 298 (25%) patients, with a total of 351 findings (1-3 per individual): 147 (42%) deletions, 106 (30%) duplications, 89 (25%) long contiguous stretches of homozygosity (LCSH) events (>5 Mb), and nine (3%) aneuploidies. Of all findings, 143 (41%) were defined as pathogenic or likely pathogenic; for another 143 findings (41%), most of which were LCSH, the clinical significance remained unknown, while 61 (18%) reported findings can now be reclassified as benign or likely benign. Clinically relevant findings were detected in 126 (11%) patients. However, the proportion of variants of unknown clinical significance was quite high (41% of all findings). It seems that our ability to detect chromosomal abnormalities has far outpaced our ability to understand their role in disease. Thus, the interpretation of CMA findings remains a rather difficult task requiring a close collaboration between clinicians and cytogeneticists.
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http://dx.doi.org/10.1002/mgg3.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960059PMC
March 2014

Alpha-1 antitrypsin phenotypes in patients with Klinefelter's syndrome.

J Genet 2010 Dec;89(4):485-8

Department of Human Biology and Genetics, Institute of General and Molecular Pathology, University of Tartu, Ravila Street 19, Tartu 50411, Estonia.

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http://dx.doi.org/10.1007/s12041-010-0069-zDOI Listing
December 2010

Neonatal spinal muscular atrophy type 1 with bone fractures and heart defect.

J Child Neurol 2007 Jan;22(1):67-70

Department of Pediatrics, Tartu University, 6 Lunini Street, Tartu 51014, Estonia.

The authors present the case of an infant girl with severe generalized weakness, multiple bone fractures, and heart defect. She needed mechanical ventilation from birth. Radiographs showed mid-diaphyseal fractures of both humeri and of the right femur as well as generalized osteopenia. Electroneuromyography showed spontaneous fibrillations at rest with no active movements. Motor response to a stimulus could not be registered. A systolic heart murmur was detected, and echocardiography showed a large atrial septal defect and an additional membrane in the left atrium. DNA analysis confirmed the diagnosis of spinal muscular atrophy on the third day of life. Histology of the muscle showed both hypertrophic and atrophic fibers. Degenerating swollen neurons were found in the ventral horns of the spinal cord and also in the mesencephalic red nucleus, which has not been described before. Humeral bone showed only partly formed cortical bone. The spectrum of spinal muscular atrophy is very diverse, and atypical clinical findings do not always rule out 5q spinal muscular atrophy. The SMN1 gene should still be investigated.
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http://dx.doi.org/10.1177/0883073807299954DOI Listing
January 2007

Descriptive epidemiology of spinal muscular atrophy type I in Estonia.

Neuroepidemiology 2006 ;27(3):164-8

Department of Paediatrics, Tartu University, Tartu, Estonia.

Spinal muscular atrophy is the second most frequent autosomal-recessive disorder in Europeans. There are no published epidemiological data on SMA in Estonia and other Baltic countries. The aim of this study was to estimate the incidence of SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and December 2003 were included in the study. The diagnosis was established on the basis of neurological evaluation, ENMG findings, molecular studies and muscle biopsy. PCR and restriction enzyme analysis was used to detect the homozygous deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live births, which is similar to the result from Hungary but lower than average incidence in the world. Only one of the patients was female. Typical SMN1 gene deletion was found in all cases.
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http://dx.doi.org/10.1159/000096128DOI Listing
December 2006