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Friedreich ataxia
Friedreich's
ataxia (FRDA) is an autosomal recessive congenital disease that causes
progressive damage to the nervous system resulting in symptoms ranging from
gait disturbance and speech problems to heart disease.
Friedreich's ataxia type 1 (
MIM: 229300) is
caused by a mutation in FXN gene
that code for frataxin, essential for proper functioning of mitochondria. Nerve
and muscle cells appear to be particularly sensitive to the deleterious effects
of this type of mitochondrial dysfunction. Although in a few pedigrees, point
mutations have been detected in FXN,
in most cases, the mutant gene contains expanded GAA triplet repeats in the
first intron that causes gene silencing through induction of a heterochromatin
structure in a manner similar to position-effect variegation.
Another locus for the disorder has been mapped to chromosome 9p (FRDA2;
MIM: 601992). In India, the
overall prevalence of FRDA is lower than that of the European countries.
This database presently holds the relevant data for Friedreich ataxia Type 1 only.
Huntington Disease (
MIM: 143100)
Huntington's
disease (HD) is an autosomal dominant disease that results from genetically
programmed degeneration of neurons, in certain areas of the brain especially
the striatum of the basal ganglia. This degeneration causes uncontrolled
movements, loss of intellectual faculties, and emotional disturbances. Also the
brain's outer surface or cortex is affected, which controls thought,
perception, and memory. HD is the most common genetic cause of abnormal
involuntary writhing movements called chorea and is much more common in people
of Western European descent than in those from Asia or Africa. HD is caused by
trinucleotide repeat (CAG) expansion in the Huntingtin gene (HTT)
leading to an increment of length of a polyglutamine stretch beyond a
threshold. It is thought that HD may be relatively frequent in India, Turkey,
and Central Asia; however, it is relatively rare in China and Japan.
Lafora Disease (
MIM: 254780)
Lafora
Disease is an autosomal recessive disorder characterized by the presence of
inclusion bodies, known as Lafora bodies, within neurons and the cells of the
heart, liver, muscle, and skin. Most patients with the disease die within the
age of twenty five. Symptoms of Lafora disease like seizures, drop attacks,
myoclonus, ataxia, and severe dementia begin to manifest themselves in children
from 10 to 17 years old and death within ten years of symptoms is usually
inevitable. To date, there is no cure or treatment for this disease. The
disease is caused by mutations in one of two known genes,
EPM2A (codes for the protein laforin) and
EPM2B (codes the protein malin).
Parkinson Disease (
MIM: 168600)
Parkinson's
disease (PD), belonging to a group of conditions called ‘movement disorders’,
is a complex neurodegenerative disease impairing the sufferer's motor skills,
speech, and other functions. Parkinson's disease is characterized by muscle
rigidity, tremor, a slowing of physical movement (bradykinesia) and a loss of
physical movement (akinesia) in extreme cases. At least, 5-10% of PD patients
are known to have monogenic forms of the disease. The identified genes are
Alpha-synuclein (SNCA), ubiquitin
carboxy-terminal hydrolase L1 (UCH-L1),
parkin (PRKN), leucine-rich repeat
kinase 2 (LRRK2 or dardarin) ,
PINK 1, DJ-1 and
ATP13A2. Many genes act as risk factors for sporadic cases of the
disease. Prevalence varies greatly throughout the world, ranging from
14/100,000 in China to 328/100,000 in Bombay, India. Asians and African blacks
have a lower incidence compared to American blacks and, especially , whites.
According to a new study, India is among the countries where the incidence of
Parkinson's disease is expected to double in the next generation--
by 2030.
The database holds the data for Parkin and PINK1 associated Parkinson’s cases.
Spinocerebellar ataxia
Spinocerebellar
ataxia (SCA) is a group of neurodegenerative genetic disorders characterized by
slowly progressive incoordination of gait and often associated with poor
coordination of hands, speech, and eye movements.
SCA
can be of multiple types, each of which could be considered a disease in its
own right
and usually, the "type" number of "SCA" refers to the order in which the gene
was found.
Persons with spinocerebellar ataxia experience a degeneration of the spinal
cord and the cerebellum, the small fissured mass at the base of the brain,
behind the brain stem.
Frequently, atrophy of the cerebellum occurs, and different ataxias are known
to affect different regions within the cerebellum.
SCA can be inherited both in a dominant and a recessive mode depending upon the
type. Many of the different SCAs fall
under the category of polyglutamine diseases
i.e. the common genetic defects is an expansion of a CAG triplet repeat.
In most of the SCAs, the glutamine repeat threshold is approximately 35, except
for SCA3 and SCA 12 (>50).
There is no known cure for SCA although not all types cause equally severe
disability.
This database presently holds the relevant data for SCA1 (
MIM: 164400);
SCA2 (
MIM: 183090),
SCA3 (
MIM: 109150), SCA6 (
MIM: 183086); SCA7 (
MIM: 164500) and SCA12 (
MIM: 604326).
Wilson Disease (
MIM: 277900)
Wilson disease (WD) is an autosomal recessive disorder caused by defects in the
copper-transporting P-type ATPase gene (ATP7B) resulting in accumulation
of copper in the liver and the brain. Wilson’s disease is diagnosed on the
basis of biochemical and clinical indicators like low serum concentrations of
ceruloplasmin, increased excretion of urinary copper, and presence of the
Kayser–Fleischer (K-F) ring. The manifestation of WD appears at a median age of
12 to 23 years. The traditional treatment for WD is based on copper chelation
with agents like penicillamine and zinc acetate. The use of agents such as
trientine and ammonium tetrathiomolybdate has also been advocated. Globally,
the disease frequency is estimated to be between 1 in 5,000 and 1 in 30,000,
and the carrier frequency is approximately 1 in 90.
Menkes Disease (
MIM: 309400)
It
is a disorder that affects copper levels in the body, leading to copper
deficiency. It is an x-linked recessive disorder, and is therefore considerably
more common in males. It is expressed in infancy and characterized by sparse
and coarse hair, growth failure, and deterioration of the nervous system (weak
muscle tone, sagging facial features, seizures, mental retardation), and
developmental delay. The patients have brittle hair and metaphyseal widening.
Mutations in the ATP7A gene on chromosome Xq13 cause Menkes syndrome. As
the result of a mutation in the ATP7A gene, copper is poorly distributed to
cells in the body. Copper accumulates in some tissues, such as the small
intestine and kidneys, while the brain and other tissues have unusually low
levels.
Rett Syndrome (
MIM: 312750)
Rett syndrome is a neurodevelopmental disorder that occurs almost
exclusively in females. Rett syndrome (RTT) is caused by mutation in the gene
encoding methyl-CpG-binding protein-2 (MECP2). It affects the development
of the central nervous system (grey matter). The
clinical features include small hands and feet and a deceleration of the rate
of head growth (including microcephaly in some), repetitive hand movements
(such as mouthing or wringing). Girls with Rett syndrome are prone to
gastrointestinal disorders and up to 80% have seizures.
Rett syndrome is usually sporadic, caused (95% or more) by a de novo mutation in
the child.
Autosomal recessive hereditary neuropathy (Charcot-Marie-Tooth disease, type 4B1) (
MIM: 601382)
Charcot-Marie-Tooth
disease type 4B1 is an autosomal recessive neurologic disorder exhibiting motor
and sensory demyelinating neuropathy with the presence of focally folded myelin
sheaths. It is caused by mutation in the gene MTMR2 mapped to chromosome 11q.
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