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A random Abstract
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Our Team
Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
[kabuki syndrome]
We
demonstrate
the
successful
application
of
exome
sequencing
to
discover
a
gene
for
an
autosomal
dominant
disorder
,
Kabuki
syndrome
(
OMIM
%
147920
)
.
We
subjected
the
exomes
of
ten
unrelated
probands
to
massively
parallel
sequencing
.
After
filtering
against
existing
SNP
databases
,
there
was
no
compelling
candidate
gene
containing
previously
unknown
variants
in
all
affected
individuals
.
Less
stringent
filtering
criteria
allowed
for
the
presence
of
modest
genetic
heterogeneity
or
missing
data
but
also
identified
multiple
candidate
genes
.
However
,
genotypic
and
phenotypic
stratification
highlighted
MLL
2
,
which
encodes
a
Trithorax-group
histone
methyltransferase
:
seven
probands
had
newly
identified
nonsense
or
frameshift
mutations
in
this
gene
.
Follow-up
Sanger
sequencing
detected
MLL
2
mutations
in
two
of
the
three
remaining
individuals
with
Kabuki
syndrome
(
cases
)
and
in
26
of
43
additional
cases
.
In
families
where
parental
DNA
was
available
,
the
mutation
was
confirmed
to
be
de
novo
(
n
=
12
)
or
transmitted
(
n
=
2
)
in
concordance
with
phenotype
.
Our
results
strongly
suggest
that
mutations
in
MLL
2
are
a
major
cause
of
Kabuki
syndrome
.