Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations

Am J Med Genet A. 2004 Jan 1;124A(1):1-9. doi: 10.1002/ajmg.a.20272.


Mutations in SLC26A4 cause Pendred syndrome, an autosomal-recessive disorder characterized by sensorineural deafness and goiter, and DFNB4, a type of autosomal recessive nonsyndromic deafness in which, by definition, affected persons do not have thyromegaly. The clinical diagnosis of these two conditions is difficult, making mutation screening of SLC26A4 a valuable test. Although screening can be accomplished in a variety of ways, all techniques are not equally accurate, timely or cost effective. We found single-strand conformational polymorphism analysis (SSCP) to be 63% effective in detecting mutations a panel of different SLC26A4 allele variants when compared to data from direct sequencing. Because direct sequencing can be time consuming and expensive, especially for a gene with 21 exons, we studied DHPLC as an alternative screening method. We found DHPLC as accurate and reliable as direct sequencing but to be more rapid and cost effective. In addition, we report 11 novel disease-causing allele variants of SLC26A4.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Transport
  • Carrier Proteins / genetics*
  • Chromatography, High Pressure Liquid
  • DNA Mutational Analysis*
  • DNA Primers
  • Diagnosis, Differential
  • Genetic Testing*
  • Goiter / diagnosis*
  • Goiter / genetics*
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Membrane Transport Proteins*
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Sulfate Transporters
  • Sulfates
  • Syndrome


  • Carrier Proteins
  • DNA Primers
  • Membrane Transport Proteins
  • SLC26A4 protein, human
  • Sulfate Transporters
  • Sulfates