Genetics defect in GJB2 and mDNA

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Transcript Genetics defect in GJB2 and mDNA

Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, MASA
What is deafness:
Genetic testing:
Partial or complete loss of hearing
The level of hearing impairment is determined by the
intensity of sound (measured in decibels (dB)).
Depending on the level of decibels lost, hearing
impairment can be divided into mild, moderate, severe
and complete or profound deafness
Hearing impairment is the most common sensory deficit
in humans.
Approximately 1 in 1000 newborns is affected by severe
to profound deafness at birth.
Additionally 1 in 1000 children progressively develops
hearing loss during childhood. With the age hearing loss
progressively increases, so that over 50% of individuals
above 80 years of age are affected
Types and causes of hearing loss:
Deafness is influenced by both genetic and
environmental factors, with inherited causes defined as the
most prominent etiological factor in deafness in developed
When associated with other symptoms it is referred as
syndromic hearing loss (SHL), while when occur as an
isolated symptom it is referred as non-syndromic hearing
loss (NSHL). NSHL accounts about 70% of genetic deafness
and is almost exclusively monogenic and highly
heterogeneous . NSHL can be transmitted as autosomal
recessive (80%), autosomal dominant (20%), X-linked
deafness and mitochondrial fashion (2%). The autosomalrecessive forms of deafness are generally the most severe
and are almost exclusively caused by cochlear defects of
hair cells (sensoryneural deafness). Autosomal-dominant
forms of deafness are usually post-lingual and progressive.
Genetics :
Detection of point mutations/small
deletions/insertions in the GJB2 gene using DNA
sequencing method
Aminoglycoside induces deafness (5 mtDNA
Detection of point mutations/small
deletions/insertions in the SLC26A4 gene using
DNA sequencing method
Detection of point mutations/small
deletions/insertions in the SLC26A4 gene using
DNA sequencing method
Benefits of Genetic Testing:
Accurate determination of the etiology of the patient's
hearing loss.
 Reduction of the need for further invasive diagnostic
 Basis
for clinical prognosis, potential medical
 Guidance regarding treatment and long-term medical
management, particularly in the young infant.
 Definitive information to guide genetic counseling of
The genetic basis of hearing loss is complex. To date,
42 different genes have been found implicated in autosomal
recessive NSHL. Mutations in some of these genes, such as
GJB2, MYO7A, CDH23, OTOF, SLC26A4, TMC1, are quite
common and can be tested in individuals with hearing loss.
Mutations in many other genes are extraordinarily rare,
some of which have been reported in only one or two
consanguineous families.
Analyses performed at RCGEB
“Georgi D. Efremov”
Elucidation of the genetic basis of hearing loss is
crucial for management of patients and their families.
Therefore, genetic testing is recommended as an integral
part of the evaluation of children with permanent hearing
Mutations in the GJB2 gene (13q12) are the most
common cause of sporadic and recessive NSHL, in many
populations worldwide. More than 100 different mutations
in this gene have been described with specific prevalence
in different ethnic groups and geographic regions. In
Caucasians the most common mutation is 35delG, while
W24X is frequent among Gypsies.
Pendred syndrome, the most common syndromic form
of deafness, is an autosomal recessive disorder associated
with developmental abnormalities of the cochlea,
sensoryneural hearing loss, and diffuse thyroid
enlargement (goiter)
Mutations in mitochondrial DNA (mtDNA) are found to
contribute to sensoryneural deafness, including both
syndromic and non-syndromic forms. Hot spot regions for
deafness mutations are the MTRNR1 gene and the MTTS1
gene. Nucleotide changes are observed with a variable
frequency among different populations of deaf persons.
OTOF-related deafness (DFNB9 nonsyndromic
hearing loss) is characterized by two phenotypes:
prelingual nonsyndromic hearing loss and, less frequently,
temperature-sensitive nonsyndromic auditory neuropathy.
The nonsyndromic hearing loss is bilateral severe-toprofound congenital deafness.
1. Online Mendelian Inheritance in Man,;
2. Sukarova Stefanovska E., Momirovska A., Cakar M., Efremov
G.D. GJB2 mutations in non syndromic hearing loss in the
Republic of Macedonia. Balkan Journal of Medical Genetics,
2009, 12(2): 11-17
3. Sukarova Stefanovska E., Cakar M., Filipce I., Plaseska
Karanfilska D. Genetics of nonsyndromic hearing loss in the
Republic of Macedonia. BJMG, 15, Suppl., 2012
RCGEB, 2013