1 Section IV. Building 22.4/24.4, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
An algorithm to investigate genetic causes in pediatric patients
Abstract Purpose: The present study was initiated to establish the etiological causes of early onset hearing loss (HL) among Estonian children between 2000-2009. Methods: The study group consisted of 233 probands who were first tested with an arrayed primer extension assay, which covers 199 mutations in 7 genes (GJB2, GJB6, GJB3, SLC26A4, SLC26A5 genes, and two mitochondrial genes - 12S rRNA, tRNASer(UCN)). From probands whose etiology of HL remained unknown, DNA analysis of congenital cytomegalovirus (CMV) infection and G-banded karyotype and/or chromosomal microarray analysis (CMA) were performed. Results: In 110 (47%) cases, the etiology of HL was genetic and in 5 (2%) congenital CMV infection was diagnosed. We found mutations with clinical significance in GJB2 (100 children, 43%) and in 2 mitochondrial genes (2 patients, 1%). A single mutation in SLC26A4 gene was detected in 5 probands (2.2%) and was considered diagnostic. In 4 probands a heterozygous IVS2-2A>G change in the SLC26A5 gene was found. We did not find any instances of homozygosity for this splice variant in the probands. CMA identified in 4 probands chromosomal regions with the loss of one allele. In 2 of them we were able to conclude that the found abnormalities are definitely pathogenic (12q13.3-q14.2 and 17q22-23.2 microdeletion), but the pathogenity of 2 other findings (3p26.2 and 1p33 microdeletion) remained unknown. Conclusion: This practical diagnostic algorithm confirmed the etiology of early onset HL for 115 Estonian patients (49%). This algorithm may be generalized to other populations for clinical application.
Advances in Medical Sciences, 2013, Vol 58, Issue 2, p. 419-28