Diagnostic criteria for Christianson Syndrome Faithful cell division requires tightly controlled protein placement at the centromeres

1. S A R A A R A N G O V A L E N C I A
M E D I C I N E S T U D E N T
Faithful cell division
requires tightly
controlled protein
placement at the
centromeres and
Diagnostic criteria for
Christianson Syndrome.

2. 1. Whitehead Institute for
Biomedical Research. "Faithful
cell division requires tightly
controlled protein placement at
the centromeres." ScienceDaily.
Science Daily, 17 July 2014
<www.sciencedaily.com/releases
/ 0107/140717124517.htm>.
2. Brown University. "Diagnostic
criteria for Christianson
Syndrome." ScienceDaily.
ScienceDaily, 21 July 2014.
<www.sciencedaily.com/releases
/2014/07/140721100416.htm>.
Faithful cell division
requires tightly controlled
protein placement at the
centromeres and Diagnostic
criteria for Christianson
Syndrome.
Molecular
biology
Teacher:
Lina Maria Martinez
Sanches
Sara Arango
Valencia
Medicine student
3rd semester
July28, 2014
CENP-A is an important
centromeric protein that
ensures a normal mitotic
division. Ranks Histone H3
in the nucleosome chromatin
at kinetochore level, so it’s
implicated in the correct
chromosomal segregation
and distribution during the
phases of mitosis.
Medical Utility
Bibliography
The CS, even though it ‘s a
little known disease, can
provide important
information about autism
because it’s highly related to
this pathology

3. A new study provides the most
definitive characterization of the
autism-like intellectual disability
disorder Christianson Syndrome
and provides the first diagnostic
criteria to help doctors and
families identify and understand
the condition. Initial evidence
suggests CS could affect tens of
thousands of boys worldwide
Faithful cell division requires tightly
controlled protein placement at the
centromeres
There are about 30 billion, and in every mitosis,
the initial DNA should be divided precisely
between two resulting cells. Many copies of the
CNP-A protein protects the centromere .
The cell's DNA is copied and condensed into
chromosomes paired, and need to secure a copy of
this protein for each. Although this rehearing of
CNP-A occurs in the G1 phase, and remains a
mystery.
Kara McKinley,'ve identified the molecular
controls that ensure that CENP-A deposition at
centromeres occurs in the right place and the right
time. Microtubules extending from opposite sides
of the cell and attached to the kinetochore, which is
anchored by molecules CENP-A at the centromere.
This allows the printing of the centromeres during
mitosis phases. If many or few chromosomes have
centromeres, or they are in the wrong place,
chromosome segregation fails, and the cell dies or
becomes ill.
McKinley found that two kinases - Plk1 and CDK –
are in charge of the correct rehearing of CENP-A,
so, the protein fills every empty space in the
centromere. Through these kinases, McKinley was
able to disrupt the replenishment of CENP-A and
cause severe problems for the segregation.
"Kara's work defined the basic control
replenishing of CENP-A" says Cheeseman,
professor at Massachusetts Institute of Technology.
"Since this step is a vital part of a centromere, his
work is a major advance in the way we think about
it as a process."
The CENP-A integrated into human
DNA at the centromeres on each
chromosome, has a vital role in cell
division. New work describes how
the tightly controlled replenishment
of CENP-A progresses. "The
assumption was that the timing of
CENP-A replenishment had to be
important for centromeres function
because it was so tightly controlled.
INTRODUCTION
Christianson Syndrome was only first
reported in 1999 and some symptoms take
more than a decade to appear, families
and doctors urgently need fundamental
information about it. A new study that
doubles the number of cases now
documented in the scientific literature
provides the most definitive
characterization of CS to date. The authors
therefore propose the first diagnostic
criteria for the condition.
In conducting their study, which includes
detailed behavioral, medical and genetic
observations of 14 boys with CS from 12
families, the team of scientists and physicians
worked with families of the small but fast-
growing Christianson Syndrome Association.
In their study, Morrow's team was able to
quantify the most frequent symptoms specific
to CS. These include intellectual disability,
epilepsy, difficulty or inability walking and
talking, attenuated head and brain growth, and
hyperactivity. Boys sometimes exhibit other
symptoms -including autism-like behaviors-
that the researchers include as secondary
proposed diagnostic criteria.
Morrow said there’s evidence that SLC9A6
mutations - and therefore CS - may be a
relatively common source of X-linked
intellectual disability.
Diagnostic criteria for
Christianson Syndrome
My opinion: This protein is not only important to
protect the centromere, it provides a succesfull
mitosis; wich is primordial for evade some patologies
My opinion: I think that is still much to
discover about the disease and its treatment.
And medicine need to improve the way of life
of this people.

4. A new study provides the most
definitive characterization of the
autism-like intellectual disability
disorder Christianson Syndrome
and provides the first diagnostic
criteria to help doctors and
families identify and understand
the condition. Initial evidence
suggests CS could affect tens of
thousands of boys worldwide
The CENP-A integrated into human
DNA at the centromeres on each
chromosome, has a vital role in cell
division. New work describes how the
tightly controlled replenishment of
CENP-A progresses. "The assumption
was that the timing of CENP-A
replenishment had to be important for
centromeres function because it was so
tightly controlled.
INTRODUCTION
En la mitosis se requiere la proteína
CENP-A que se depositará en el
lugar correcto. Cuando las dos
quinasas responsables de la
regulación de este proceso - CDK y
Plk1 - están bloqueados, las células
en división tienen defectos mitoticos
graves, incluyendo mal alineamiento
cromosomico y husos multipolares,
en comparación con las células
normales.
A new study of 14 boys with CS of 12
families of the Christianson
Syndrome Association, the team of
scientists. In their study, Morrow's
team was able to quantify the most
frequent symptoms specific to CS.

5. Faithful cell division requires tightly controlled
protein placement at the centromeres
There are about 30 billion, and in every mitosis, the initial DNA should be divided
precisely between two resulting cells. Many copies of the CNP-A protein protects the
centromere .
The cell's DNA is copied and condensed into chromosomes paired, and need to secure
a copy of this protein for each. Although this rehearing of CNP-A occurs in the G1
phase, and remains a mystery.
Kara McKinley,'ve identified the molecular controls that ensure that CENP-A
deposition at centromeres occurs in the right place and the right time. Microtubules
extending from opposite sides of the cell and attached to the kinetochore, which is
anchored by molecules CENP-A at the centromere. This allows the printing of the
centromeres during mitosis phases. If many or few chromosomes have centromeres,
or they are in the wrong place, chromosome segregation fails, and the cell dies or
becomes ill.
McKinley found that two kinases - Plk1 and CDK – are in charge of the correct
rehearing of CENP-A, so, the protein fills every empty space in the centromere.
Through these kinases, McKinley was able to disrupt the replenishment of CENP-A
and cause severe problems for the segregation.
"Kara's work defined the basic control replenishing of CENP-A" says Cheeseman,
professor at Massachusetts Institute of Technology. "Since this step is a vital part of a
centromere, his work is a major advance in the way we think about it as a process."
My opinion: This protein is not only important to protect
the centromere, it provides a succesfull mitosis; wich is
primordial for evade some patologies
Faithful cell division requires tightly controlled protein placement at
the centromeres
Whitehead Institute for Biomedical Research
July 17, 2014

6. Faithful cell division requires tightly controlled protein placement at
the centromeres
Whitehead Institute for Biomedical Research
July 17, 2014
 Images of cells with normal and
abnormal CENP-A deposition.
Centromere (red) location and proper
division of chromosomes (blue) by
microtubules (green) in mitosis require
the protein CENP-A to be deposited in
the correct place. When the the two
kinases responsible for regulating this
process--CDK and Plk1--are blocked,
dividing cells have severe mitotic
defects, including dramatically
misaligned chromosomes and
multipolar spindles (right), compared
to normal cells (left).

7.  During division of any of the body's
roughly 30 trillion cells, DNA from
the initial cell must be split
precisely between the two resulting
cells. Critical to successful cell
division is the integrity of the
centromere
Faithful cell division requires tightly controlled protein placement at
the centromeres
Whitehead Institute for Biomedical Research
July 17, 2014
 For the segregation machinery to
recognize this region, it must
contain many copies of a pivotal
protein known as CENP-A.
 Each time the cell makes a copy of
its DNA in preparation for cell
division, it needs to ensure that the
centromeres of the new and old
DNA strand get re-filled with
CENP-A.

8.  Cheeseman's lab has identified
the molecular controls that
ensure that CENP-A deposition
at centromeres occurs in the
right place at precisely the right
time.
 The fate of the cell depends on
this process going smoothly. If
the chromosomes have too
many or too few centromeres,
or the centromeres are located
in the wrong place, proper
chromosome segregation fails
Faithful cell division requires tightly controlled protein placement at
the centromeres
Whitehead Institute for Biomedical Research
July 17, 2014

9. My opinion: This protein is
not only important to protect
the centromere, it provides a
succesfull mitosis; wich is
primordial for evade some
patologies
Faithful cell division requires tightly controlled protein placement at
the centromeres
Whitehead Institute for Biomedical Research
July 17, 2014

10. Diagnostic criteria for Christianson Syndrome
Brown University
July 21, 2014
Christianson Syndrome was only first reported in 1999 and some
symptoms take more than a decade to appear, families and doctors
urgently need fundamental information about it. A new study that
doubles the number of cases now documented in the scientific
literature provides the most definitive characterization of CS to date.
The authors therefore propose the first diagnostic criteria for the
condition.
In conducting their study, which includes detailed behavioral, medical
and genetic observations of 14 boys with CS from 12 families, the team
of scientists and physicians worked with families of the small but fast-
growing Christianson Syndrome Association.
In their study, Morrow's team was able to quantify the most frequent
symptoms specific to CS. These include intellectual disability, epilepsy,
difficulty or inability walking and talking, attenuated head and brain
growth, and hyperactivity. Boys sometimes exhibit other symptoms -
including autism-like behaviors- that the researchers include as
secondary proposed diagnostic criteria.
Morrow said there’s evidence that SLC9A6 mutations - and therefore CS
- may be a relatively common source of X-linked intellectual disability.
Diagnostic criteria for Christianson Syndrome
My opinion: I think that is still much to discover about the
disease and its treatment. And medicine need to improve the
way of life of this people.

11. These scans show atrophy of the cerebellum in a boy with
Christianson Syndrome. This symptom was observed in some, but not
all boys, with the condition.
Diagnostic criteria for Christianson Syndrome
Brown University
July 21, 2014

12.  Morrow's team was able to quantify the
most frequent symptoms specific to CS.
These include moderate to severe
intellectual disability, epilepsy,
difficulty or inability walking and
talking, attenuated head and brain
growth, and hyperactivity.
 Many CS traits, including a very happy
disposition, appear similar to those of
another autism-like condition,
Angelman Syndrome, but the study
defines important differences.
Tagged Christianson syndrome. The image shows the
neural growth.
 Boys have a mutation on the SLC9A6
gene on the X chromosome that disables
production of a protein called NHE6 that
is important for neurological
development.
 Girls, who have two X chromosomes, can
also be carriers of CS mutations, but they
appear to be affected differently and less
severely or not at all, the study reports.
Diagnostic criteria for Christianson Syndrome
Brown University
July 21, 2014

13.  "If we assume that between 1-3
percent of the world's
population is diagnosed with an
intellectual disability and
approximately 10-20 percent of
the causes are due to X-linked
genes, then we can estimate
that CS may affect between 1 in
16,000 to 100,000 people"
 The connection to the SLC9A6
gene was first discovered in 2008.
In analyzing the genomes of each
patient and their parents in the
new study, they found that each
boy had only one mutation, but
there were many different ones
across the entire group.
Diagnostic criteria for Christianson Syndrome
Brown University
July 21, 2014

14. Diagnostic criteria for
Christianson Syndrome
Brown University
July 21, 2014
In a paper published
last year, Morrow's
research group found
that NHE6 is
underexpressed in the
brains of many children
with more general
forms of autism. This
potential connection
suggests that learning
about CS can help
doctors and scientists
learn about autism.

15. Diagnostic criteria for Christianson Syndrome
Brown University
July 21, 2014
My opinion: I think that is
still much to discover about the
disease and its treatment. And
medicine need to improve the
way of life of this people.

16. CENP-A is an important
centromeric protein that
ensures a normal mitotic
division. Ranks Histone H3
in the nucleosome chromatin
at kinetochore level, so it’s
implicated in the correct
chromosomal segregation
and distribution during the
phases of mitosis.
Medical Utility
The CS, even though it ‘s a
little known disease, can
provide important
information about autism
because it’s highly related to
this pathology

17. CENP-A is an
important
centromeric protein
that ensures a
normal mitotic
division. Ranks
Histone H3 in the
nucleosome
chromatin at
kinetochore level, so
it’s implicated in the
correct chromosomal
segregation and
distribution during
the phases of mitosis.
Medical Utility
This protein allows to know more
thoroughly mitosis, and that such an
accurate distribution of chromosomes in the
process is given.

18. CENP-A is an
important
centromeric protein
that ensures a
normal mitotic
division. Ranks
Histone H3 in the
nucleosome
chromatin at
kinetochore level, so
it’s implicated in the
correct chromosomal
segregation and
distribution during
the phases of mitosis.
Medical Utility
CENP-A is a protein with wich one
you can differentiate centromeric
DNA of another parts of the
chromosome

19. The CS, even though it ‘s a little
known disease, can provide
important information about
autism because it’s highly
related to this pathology
Medical Utility
The SLC9A6 gene on Xq26.3 encodes the
Na+/H+ exchanger, NHE6. This testing is
useful to confirm the diagnosis and to
identify the disease causing mutation within
a family to allow for carrier testing and
prenatal diagnosis.

20. The CS, even though it ‘s a little
known disease, can provide
important information about
autism because it’s highly
related to this pathology
Medical Utility
"We can now study these different mutations and
learn how this protein works by how it gets
inactivated," he said. "All the different ways it gets
inactivated can actually inform us about the different
components of the protein that have an important
function."

21. • W H I T E H E A D I N S T I T U T E F O R B I O M E D I C A L R E S E A R C H .
" F A I T H F U L C E L L D I V I S I O N R E Q U I R E S T I G H T L Y C O N T R O L L E D
P R O T E I N P L A C E M E N T A T T H E C E N T R O M E R E S . "
S C I E N C E D A I L Y . S C I E N C E D A I L Y , 1 7 J U L Y 2 0 1 4 .
< W W W . S C I E N C E D A I L Y . C O M / R E L E A S E S / 2 0 1 4 / 0 7 / 1 4 0 7 1 7 1 2 4 5 1 7 .
H T M > .
• B R O W N U N I V E R S I T Y . " D I A G N O S T I C C R I T E R I A F O R
C H R I S T I A N S O N S Y N D R O M E . " S C I E N C E D A I L Y . S C I E N C E D A I L Y ,
2 1 J U L Y 2 0 1 4 .
< W W W . S C I E N C E D A I L Y . C O M / R E L E A S E S / 2 0 1 4 / 0 7 / 1 4 0 7 2 1 1 0 0 4 1 6
. H T M > .
BIBLIOGRAPHY

22. GRACIAS!!!