Diagnostics Service of
the Molecular Otolaryngology & Renal Research Laboratories is a Joint
Commission-approved CLIA-accredited diagnostic laboratory that
offers mutation screening of several genes.
DFNB4 (OMIM#: 600791)
and Pendred syndrome (OMIM#: 274600)
Baldwin and colleagues reported linkage of a
family with recessive, nonsyndromic deafness to chromosome 7q31
in 1995 and designated this locus as DFNB4. Mutations in SLC26A4 are
causally related to deafness at this locus. Inner ear computed
tomography has shown that DFNB4 includes dilation of the
endolymphatic duct (DVA, also called enlarged vestibular
aqueduct syndrome, EVA [OMIM# 600791]).
Pendred syndrome (OMIM#: 274600)
is a common syndromic form of hearing loss (Fraser 1965).
Clinical features include inner ear abnormalities, sensorineural
hearing loss and diffuse thyroid enlargement or goiter. Inner
ear computed tomography has shown that the Pendred Syndrome
phenotype includes dilation of the endolymphatic duct and sac,
enlargement of the vestibular aqueduct and cochlear dysplasia.
This constellation of anomalies is known as Mondini malformation
or Mondini dysplasia.
Mutations in SLC26A4 (OMIM#: 605646)
cause Pendred Syndrome. Over 150 mutations have been described (http://www.healthcare.uiowa.edu/labs/pendredandbor/).
The gene is a member of the solute carrier gene family and
functions as an anion carrier. It has 21 exons and the encoded
protein, called Pendrin, has 780 amino acids.
MORL screening methodology
Oligonucleotide primers have been designed for amplification of each exon including intron/exon boundaries of
SLC26A4. These amplimers are used for bi-directional sequencing.
Sensitivity is greater than 99%.
Turn around time is approximately 8 weeks
(Average TAT - 59 days).
Indications for screening
This test is appropriate for any person with
congenital sensorineural hearing loss and an inner ear
abnormality by computed tomography (DVA, EVA, Mondini dysplasia).
GeneTests GeneReviews –
Pendred, V.: Deaf
mutism and goitre.Lancet. 1896;ii:532.
Fraser, G. R. : Association
of congenital deafness with goiter (Pendred's syndrome): a study
of 207 families. Ann.
Hum. Genet. 28: 201-249, 1965.
PubMed ID: 14304636
Campbell, C. et al.: Pendred
syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel
mutations and possible genotype-phenotype correlations. Hum.
Mutat. 17: 403-411, 2001.
PubMed ID: 11317356
Prasad, S. et al.: Pendred
syndrome and DFNB4-mutation screening of SLC26A4 by denaturing
high-performance liquid chromatography and the identification of
eleven novel mutations.
J. Hum. Genet. 2004 Jan 1;124(1):1-9.
PubMed ID: 14679580
Pendred and BOR Homepage: http://www.medicine.uiowa.edu/pendredandbor/