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- Title
The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity.
- Authors
Pajusalu, Sander; Žilina, Olga; Yakoreva, Maria; Tammur, Pille; Kuuse, Kati; Mölter-Väär, Triin; Nõukas, Margit; Reimand, Tiia; Õunap, Katrin
- Abstract
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. © 2015 S. Karger AG, Basel
- Publication
Molecular Syndromology, 2015, Vol 6, Issue 3, p135
- ISSN
1661-8769
- Publication type
Article
- DOI
10.1159/000438776