ABSTRACT
Background
Sensorineural
hearing
loss
(SNHL)
is
a
frequent
manifestation
of
syndromic
inherited
retinal
diseases
(IRDs),
exemplified
by
the
very
rare
form
autosomal‐dominant
Leber
congenital
amaurosis
with
early
onset
deafness
(LCAEOD;
OMIM
#617879).
LCAEOD
was
first
described
in
2017
four
families
segregating
heterozygous
missense
mutations
TUBB4B
,
gene
encoding
β‐tubulin
isotype.
To
date,
only
eight
more
similar
‐associated
sensorineural
disease
(SND)
have
been
reported.
Most
cases
harbored
variants
affecting
same
amino
acid
(Arg391)
and
three
segregated
involving
different
residues
(Tyr310,
Arg390).
Methods
We
performed
whole‐exome
sequencing
full
ophthalmological
audiological
examination
affected
members
an
Italian
family
IRD
deafness.
Results
identified
novel,
ultra‐rare,
disease‐causing
variant
(NM_006088.6:c.1049A>C)
that
replaces
highly
conserved
lysine
threonine
at
position
350.
The
functional
impact
Lys350Thr
substitution
supported
protein
structure
modeling
studies.
segregates
presenting
SNHL.
Detailed
assessment
subjects
diagnosed
progressive
cone‐rod
dystrophy.
Conclusion
These
findings
expand
limited
number
variants,
corroborating
their
association
SND
forms,
suggest
Lys350
important
residue
for
function.
Interestingly,
our
results
demonstrate
can
cause
cone‐dominated
phenotypes.
Trends in Genetics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 1, 2025
HighlightsHuman
handedness
is
a
moderately
heritable
trait.Large-scale
genome-wide
association
and
exome
sequencing
studies
have
identified
multiple
genes
associated
with
highlighted
role
of
tubulin
genes.Axon
guidance,
axon
growth,
forming
the
inner
structure
motile
cilia
are
key
processes
regulated
by
that
may
also
be
relevant
for
handedness,Tubulin
several
psychiatric
disorders
which
offer
insights
into
biological
pathways
mediating
link
between
handedness,
brain
asymmetries,
disorders.AbstractHandedness
(i.e.,
preference
to
use
either
left
or
right
hand
fine
motor
tasks)
widely
investigated
trait.
Handedness
heritability
consistently
estimated
25%.
After
decades
research,
recent
large-scale
genes.
Tubulin
play
in
during
development
ontogenesis,
including
cilia.
Moreover,
disorders.
This
finding
therefore
traits.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 26, 2024
Abstract
Asymmetry
between
the
left
and
right
hemisphere
is
a
key
feature
of
brain
organization.
Hemispheric
functional
specialization
underlies
some
most
advanced
human-defining
cognitive
operations,
such
as
articulated
language,
perspective
taking,
or
rapid
detection
facial
cues.
Yet,
genetic
investigations
into
asymmetry
have
mostly
relied
on
common
variants,
which
typically
exert
small
effects
brain-related
phenotypes.
Here,
we
leverage
rare
genomic
deletions
duplications
to
study
how
alterations
reverberate
in
human
behavior.
We
designed
pattern-learning
approach
dissect
impact
eight
high-effect-size
copy
number
variations
(CNVs)
multi-site
cohort
552
CNV
carriers
290
non-carriers.
Isolated
multivariate
patterns
spotlighted
regions
thought
subserve
lateralized
functions,
including
hearing,
well
visual,
face
word
recognition.
Planum
temporale
emerged
especially
susceptible
specific
gene
sets.
Targeted
analysis
variants
through
genome-wide
association
(GWAS)
consolidated
partly
diverging
influences
versus
planum
structure.
In
conclusion,
our
gene-brain-behavior
data
fusion
highlights
consequences
genetically
controlled
lateralization
uniquely
capacities.
Trends in Genetics,
Journal Year:
2024,
Volume and Issue:
40(7), P. 558 - 559
Published: May 14, 2024
Twin
studies
suggest
that
additive
genetic
effects
account
for
about
a
quarter
of
the
variance
in
handedness.
Recently,
Schijven
et
al.
used
exome-wide
sequencing
to
provide
evidence
role
rare
protein-coding
variants
These
included
gene
encoding
beta-tubulin,
TUBB4B,
suggesting
microtubules
are
relevant
handedness
ontogenesis.
