Hearing impairment in Estonia: an algorithm to investigate genetic causes in pediatric patients

Adv Med Sci. 2013;58(2):419-28. doi: 10.2478/ams-2013-0001.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Algorithms*
  • Anion Transport Proteins / genetics
  • Child
  • Child, Preschool
  • Connexin 26
  • Connexin 30
  • Connexins / genetics*
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / genetics
  • Estonia
  • Female
  • Hearing Loss, Sensorineural / etiology*
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / virology
  • Hearing Tests
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Membrane Transport Proteins / genetics
  • RNA, Ribosomal / genetics
  • Sulfate Transporters

Substances

  • Anion Transport Proteins
  • Connexin 30
  • Connexins
  • GJB2 protein, human
  • GJB6 protein, human
  • Membrane Transport Proteins
  • RNA, Ribosomal
  • RNA, ribosomal, 12S
  • SLC26A4 protein, human
  • SLC26A5 protein, human
  • Sulfate Transporters
  • Connexin 26
  • GJB3 protein, human