Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 14, 2024
Abstract
Background:
The
ethnic
diversity
of
India
provides
a
unique
opportunity
to
study
the
history
origin
mutations
genetic
disorders.
Spinocerebellar
ataxia
type
27B
(SCA27B),
recently
identified
dominantly
inherited
cerebellar
disorder
is
caused
by
GAA-repeat
expansions
in
intron
1
Fibroblast
Growth
Factor
14
(
FGF14
).
Being
predominantly
reported
European
population,
we
aimed
screen
this
mutation
and
founder
haplotype
SCA27B
Indian
patients.
Methods
:
We
have
undertaken
screening
GAA
repeats
large
cohort
~1400
uncharacterized
patients
kindreds
long-read
sequencing
based
repeat
length
assessment.
High
throughput
genotyping
analysis
was
also
performed.
utilized
~1000
genomes
at-risk
expansion
alleles.
Findings
report
high
frequency
1.83%
(n=23)
cohort.
observed
several
biallelic
(n=5)
with
younger
onset
disease.
risk
(AATCCGTGG)
flanking
FGF4-GAA
locus
over
74
kb
region
linkage
disequilibrium.
further
studied
across
diverse
geographical
population
groups.
highest
prevalence
(29.9%)
followed
Indians
(21.5%).
has
existed
through
generations
(~28000
years),
assuming
correlated
genealogy.
Interpretation:
Through
study,
highlight
insights
gained
about
its
Caucasian
subcontinent.
Occurrence
probably
more
due
endogamous
nature
population.
The Cerebellum,
Journal Year:
2024,
Volume and Issue:
23(5), P. 2152 - 2168
Published: May 18, 2024
Abstract
The
hereditary
cerebellar
ataxias
(HCAs)
are
rare,
progressive
neurologic
disorders
caused
by
variants
in
many
different
genes.
Inheritance
may
follow
autosomal
dominant,
recessive,
X-linked
or
mitochondrial
patterns.
list
of
genes
associated
with
adult-onset
ataxia
is
continuously
growing,
several
new
discovered
the
last
few
years.
This
includes
short-tandem
repeat
(STR)
expansions
RFC1
,
causing
ataxia,
neuropathy,
vestibular
areflexia
syndrome
(CANVAS),
FGF14
-GAA
spinocerebellar
type
27B
(SCA27B),
and
THAP11
.
In
addition,
genetic
basis
for
SCA4,
has
recently
been
identified
as
a
STR
expansion
ZFHX3.
Given
large
growing
number
genes,
gene
variant
types,
approach
to
diagnostic
testing
HCA
can
be
complex.
Testing
methods
include
targeted
evaluation
(e.g.
SCAs,
Friedreich
fragile
X-associated
tremor/ataxia
syndrome,
dentatorubral-pallidoluysian
atrophy),
next
generation
sequencing
conventional
variants,
which
panels,
whole
exome,
genome
sequencing,
followed
various
potential
additional
tests.
review
proposes
clinical
testing,
highlights
challenges
current
technologies,
discusses
future
advances
overcome
these
limitations.
Implementing
long-read
transform
HCA,
overall
aim
improve
yield.
The Cerebellum,
Journal Year:
2024,
Volume and Issue:
23(5), P. 2012 - 2027
Published: May 7, 2024
Abstract
The
functional
Scale
for
the
Assessment
and
Rating
of
Ataxia
(f-SARA)
assesses
Gait,
Stance,
Sitting,
Speech.
It
was
developed
as
a
potentially
clinically
meaningful
measure
spinocerebellar
ataxia
(SCA)
progression
clinical
trial
use.
Here,
we
evaluated
content
validity
f-SARA.
Qualitative
interviews
were
conducted
among
individuals
with
SCA1
(
n
=
1)
SCA3
6)
healthcare
professionals
(HCPs)
SCA
expertise
(USA,
5;
Europe,
3).
Interviews
symptoms
signs
relevance
f-SARA
concepts
SCA.
HCP
cognitive
debriefing
conducted.
recorded,
transcribed,
coded,
analyzed
by
ATLAS.TI
software.
Individuals
3
reported
85
symptoms,
signs,
impacts
All
indicated
difficulties
walking,
stance,
balance,
speech,
fatigue,
emotions,
work.
considered
Speech
relevant
concepts;
Sitting
(42.9%).
HCPs
Gait
relevant;
5
(62.5%)
Stance
relevant.
late-stage
disease
indicator.
Most
suggested
inclusion
appendicular
items
would
enhance
relevance.
Cognitive
supported
clarity
comprehension
Maintaining
current
abilities
on
1
year
most
3.
changes
stability
in
score
over
1–2
years,
1–2-point
change
total
score,
deviation
from
natural
history.
These
results
support
assessing
trials.
Neurology and Therapy,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 13, 2025
The
Friedreich
Ataxia
Rating
Scale–Activities
of
Daily
Living
(FARS-ADL)
is
a
valid,
highly
utilized
measure
for
assessing
ADL
impacts
in
patients
with
ataxia.
We
provide
evidence
the
psychometric
validity
FARS-ADL
two
cohorts
spinocerebellar
ataxia
(SCA).
Using
data
from
cohort
real-world
subjects
SCA
(recruited
at
Massachusetts
General
Hospital
[MGH];
n
=
33)
and
phase
3
trial
troriluzole
adults
(NCT03701399
[Study
206];
217),
comprising
subset
SCA3
genotype
(n
89),
measurement
properties
minimal
change
thresholds
were
examined.
Ceiling
effects
absent
within
MGH
while
floor
observed
eight
nine
items.
Excellent
internal
consistency
reliability
was
(αtotal
0.88;
αitems−removed
0.86–0.87),
item-to-total
correlations
acceptable
(r
0.55–0.89
per
item).
Convergent
divergent
supported
strong
demonstrated
between
scales
measuring
similar
concepts
(Neuro-QOL
[Upper],
Neuro-QOL
[Lower],
PROM-ADL,
PROM-PHYS,
FARS-FUNC;
all
P
<
0.001)
weaker
shown
measures
differing
constructs.
A
two-
to
three-point
threshold
meaningful
changes
as
0.5
×
SD
2.43,
SEM
2.19.
Mean
baseline
classified
"improved,"
"no
change,"
or
"deteriorated"
−0.54,
0.22,
1.47,
respectively.
Similar
trends
Study
206
all-SCA
cohorts.
Psychometric
evaluation
showed
that
performed
well
on
analyses
examining
can
detect
SCA,
including
those
SCA3.
ClinicalTrials.gov
identifier,
NCT03701399
(Study
206).
