Publications by authors named "Triin Mölter-Väär"

2 Publications

  • Page 1 of 1

The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity.

Mol Syndromol 2015 Sep 15;6(3):135-40. Epub 2015 Aug 15.

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

We present data from our clinical department's experience with chromosomal microarray analysis (CMA) regarding the diagnostic utility of 1 or 2 long contiguous stretches of homozygosity (LCSHs) in an outbred population. The study group consisted of 2,110 consecutive patients from 2011 to 2014 for whom CMA was performed. The minimum cut-off size for defining a homozygous stretch was 5 Mb. To focus on cases with no parental consanguinity, we further studied only patients in whom the total length of homozygous stretches did not exceed 28 Mb or 1% of the autosomal genome length. We identified 6 chromosomal regions where homozygous stretches appeared in at least 3 patients and excluded these from further analysis. In 2 out of 120 patients with an isolated finding of 1 or 2 non-recurrent LCSHs, a plausible candidate gene associated with their phenotype was identified within the homozygous stretch. In both of these cases, a pathogenic mutation was detected, leading to diagnoses of pyruvate kinase deficiency and Marinesco-Sjögren syndrome. To clarify whether previously found homozygous stretches could be important for the interpretation of genome-wide sequencing data, we report 7 cases in which homozygous stretches not encompassing a clinically associated gene were first found on CMA, followed by the diagnostic whole-exome sequencing. The diagnostic utility of single LCSHs, unlikely to be caused by uniparental disomy, is discussed in detail.
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http://dx.doi.org/10.1159/000438776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698626PMC
September 2015

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