Zebrafish provide insights into a rare human disease
Scientists from the Delhi-based CSIR-Institute of Genomics and
Integrative Biology are a step closer to bringing hope to children born with a
rare disorder — CHARGE syndrome — if the results seen in
zebrafish are reproducible in humans. Scientists have studied the fertilised
egg of a zebrafish to better understand the CHARGE syndrome.
Why zebrafish?
Following fertilization, zebrafish embryos are transparent. This
allows scientists to observe the inside of the embryo and watch in real time
how various organs develop. Since most organs begin forming in the first 24-36
hours and are fully formed within five days, it allows researchers to study the
development of an organism from egg to maturity. An RNA injected into a
one-cell embryo interferes with the making of the CHD7 protein, thus producing
a zebrafish embryo with very similar problems as the human babies with CHARGE
syndrome.
Background:
About 1 in 20,000 people in the world, and an estimated 50,000 in
India alone, are born with CHARGE syndrome — multiple life-threatening problems
such as deafness and blindness, heart defects, genital problems and growth
retardation and facial bone and nerve defects that cause breathing and
swallowing difficulties. There is a high death rate in the very first year in
children born with CHARGE. A mutation in the CHD7 gene is responsible for
60-70% of all CHARGE defects. The expression of the gene peaks in the early
stages of embryo development, starting from 2-4 cells.
About CHARGE syndrome:
CHARGE syndrome is a disorder that affects many areas of the body. CHARGE stands for coloboma, heart defect,
atresia choanae (also known as choanal atresia), retarded growth and
development, genital abnormality, and ear abnormality.
- The pattern of malformations varies among individuals with this disorder, and infants often have multiple life-threatening medical conditions. About two third of cases are due to a CHD7 mutation.
- The major characteristics of CHARGE syndrome are more specific to this disorder than are the minor characteristics. Many individuals with CHARGE syndrome have a hole in one of the structures of the eye (coloboma), which forms during early development.
- Some people also have small eyes (microphthalmia). One or both nasal passages may be narrowed or completely blocked.
- Individuals with CHARGE syndrome frequently have cranial nerve abnormalities. The cranial nerves emerge directly from the brain and extend to various areas of the head and neck, controlling muscle movement and transmitting sensory information.
- Abnormal function of certain cranial nerves can cause swallowing problems, facial paralysis, a sense of smell that is diminished (hyposmia) or completely absent (anosmia), and mild to profound hearing loss. People with CHARGE syndrome also typically have middle and inner ear abnormalities and unusually shaped ears.
- The diagnosis of CHARGE syndrome is often difficult, because it is rare. The syndrome spans many disciplines, and as such, can be diagnosed by a pediatrician, oral and maxillofacial surgeon, ENT specialist, ophthalmologist, audiologist, endocrinologist, cardiologist, urologist, developmental specialist, radiologist, geneticist, physiotherapist, occupational therapist, speech therapist, or orthopedic specialist.
