More Related Content Similar to CFERV 2019 Simons Searchlight (20) More from JillianHastingsWard (11) CFERV 2019 Simons Searchlight2. What is the
goal of Simons
Searchlight?
Collect detailed
medical and
behavioral histories
along with blood
and saliva samples
Synthesize the
information you
provide and
share results
back to families
Freely share
data and
samples with
qualified
researchers
Connect
participants
around the
world
Promote better
understanding
of these
genetic
changes
© Jennifer Bain, MD, PhD
3. How has Simons Searchlight
changed over time?
• The study began in 2011 and focused
on families living with one specific
genetic change.
• The first participants traveled to study
centers to provide medical, behavioral
and neuropsychiatric data to
researchers.
• Today, families living with one of more
than 100 different genetic changes can
provide their data to researchers from
home.
© Jennifer Bain, MD, PhD
4. What do you do as a participant?
• Provide medical and behavioral
histories and samples.
• Update us annually.
• Samples can be collected locally or at
family meetings.
• All of the information is used to fuel
studies by doctors and scientists
across the globe.
© Jennifer Bain, MD, PhD
5. What are the benefits of being
involved?
• Become part of a large network of
scientists, doctors, and families united
in their goal to move research forward.
• Connect through social media,
newsletters, webinars, regular contact
with study staff, national and
international family meetings, and
more.
© Jennifer Bain, MD, PhD
6. Data
Collection
What information is collected?
Whose information is collected?
Individuals with the
genetic change
Parents Siblings
Medical records
• Clinical Genetic Lab Results X X X
Phone Interviews
• Medical History Interview
• Previous Diagnosis interview
• Adaptive functioning interview –
Vineland Adaptive Behavior
X
X
X
Online surveys
• Seizure History
• Background History
• Child/Adult Behavior Checklist
• Social Responsiveness Scale
• Social Communication
Questionnaire
• Other surveys in development
X
X
X
X
X
X
X
X
X
X
X
© Jennifer Bain, MD, PhD
7. How does the Simons Foundation
help further GRIN2B research?
Sabo
Impact of NR2B/GRIN2B
subunit mutations on
NMDA receptors and
synapse formation
• GRIN2B data and samples
available at Simons
Foundation SFARI Base
(base.sfari.org)
• Approved researchers can
use the data and samples
• The Simons Foundation
funds research on genes
that affect NMDA receptors
Fagiolini
Probing synaptic receptor
composition in mouse
models of autism
Traynelis
Functional role of rare
missense glutamate receptor
variants in neurological
disease
© Jennifer Bain, MD, PhD
8. How to link up with the new Simons Searchlight
Receive email
“Important changes to
Simons VIP - please read
for access instructions”
If you had an account on the Simons VIP Connect registry – DO THIS ASAP!!
Click link in email
“By clicking the link, you’re
agreeing to the site’s terms
and conditions and privacy
policy.
Click here to get started.”
Reset password
© Jennifer Bain, MD, PhD
10. Not all Genetic Conditions Run in Families
Some are de novo mutations
© Jennifer Bain, MD, PhD
11. When do de novo mutations occur?
• In the egg
• In the sperm
• At or shortly after conception
• No way to know
• Recurrence risk of 1% in future pregnancies
© Jennifer Bain, MD, PhD
13. 84
Registered
42
Consented and
Labs reviewed
36
pathogenic or
likely
pathogenic
31*
Medical History
by 7-1-2019
* 4 Others with different types of variants completed the MHI.
Others may have completed it after 8-16-19
Simons Searchlight Individuals with GRIN2B
Mutation
12 female, 19 male
Ages 2 - 21 years
© Jennifer Bain, MD, PhD
14. Variants in GRIN2B Observed
36 individuals with pathogenic or likely pathogenic variants
Likely gene
disrupting
mutations
Glu236*
Arg393*
Arg847* (2)
Arg926*
• 6 additional participants with non-conforming variants
Missense mutations
Gly499Glu Asn694Ser
Asn516Ser (2) Arg696His
Ser526Pro Cys746Tyr
Gly543Arg Ile751Thr (3)
Ser555Ile Leu781Val
Val558Ile Gly820Ala (3)
Gly611Val Gly820Glu
Val620Met Val821Phe
Tyr646Cys Gly826Glu (2)
Pro687Leu Glu839Lys
Gly689Ser Thr888Thr
Deletions
Intragenic deletions (2)
In-Frame Deletion/ Insertions
(Substitutions)
Arg682_Val686delinsSerPheGlyThrLeu
© Jennifer Bain, MD, PhD
15. Developmental Milestones
• 52% (12) of
children attained
first words
between age 9
months and 5
years
• 11 children
(ages 2-14
years) were not
reported to have
spoken first
words
• 68% (15) of
children attained
first steps between
age 1 and 7 years
• 7 children (ages 2-
14 years) were not
reported to have
taken first steps
First steps in 22 individualsFirst words in 23 individuals
* 4 individuals were not included
because they were too young
* 5 individuals were not included
because they were too young or had
incomplete data
Does not take into account any regressions
© Jennifer Bain, MD, PhD
16. • 25% (4) of
children attained
bladder control
between age 3
and 4 years
• 12 children (4-14
years old) were
not reported to
have gained
bladder control
• 25% (4) children
attained bowel
control between
age 2 and 4 years
• 12 children (4-14
years old) were not
reported to have
gained bowel
control
Age at bowel control in 16 individualsAge at bladder control in 16 individuals
*11 individuals were not included
because they were too young or had
incomplete data
* 11 individuals were not included
because they were too young or had
incomplete data
Does not take into account any regressions
Developmental Milestones
© Jennifer Bain, MD, PhD
17. Simons Searchlight
GRIN2B Medical History
Data
31 individuals, age 2 years - 21 years
* 4 other individuals with different types of variants also completed the MHI
© Jennifer Bain, MD, PhD
18. Common Developmental and Behavioral Diagnoses
in 29 GRIN2B participants
Condition Percent of children (n)
Intellectual disability/ developmental delay* 100% (29)
Autism spectrum disorder 28% (8)
Attention deficit/hyperactivity disorder 10% (3)
Sleep apnea 3% (1)
Dystonia 3% (1)
* 22 of whom have language impairment, disorder, or delays
© Jennifer Bain, MD, PhD
19. Language Difficulties
• Expressive,receptive or pragmatic (conversational)speech
• Poor/absent speech =motor speechdisturbance
• Apraxia of speech
• Motor planning problem between the brain and the output from your
mouth.
• Techniquesfor intervention: speechtherapy, PROMPTtherapy,
Augmentative/Alternative Communication(AAC).
© Jennifer Bain, MD, PhD
20. • Nolonger subcategories: autistic disorder,Aspergerdisorder, Rett disorder,
childhood disintegrative disorder, pervasive developmental disorder(PDD-NOS)
Corebehaviors
Persisting deficits of
social communication
and interaction
Restricted and
repetitive behaviors,
interests and
activities
Autism Spectrum Disorder (ASD)
© Jennifer Bain, MD, PhD
21. Condition Percent of children (n)
Strabismus (crossed eyes) 55% (17)
Nystagmus
(repetitive, uncontrolled eye movements) 15% (5)
Nearsighted 13% (4)
Cortical blindness 10% (3)
Farsighted 10% (3)
Ptosis (drooping upper eyelid) 3% (1)
Depth perception 3% (1)
Other (not specified) 3% (1)
Eye & Vision Problems
© Jennifer Bain, MD, PhD
22. Condition Percent of children (n)
Low muscle tone 94% (29)
Clumsy 39% (12)
High muscle tone 23% (7)
Large head size 10% (3)
Small head size 10% (3)
Movement disorder 10% (3)
Cerebral palsy 6% (2)
Tics 3% (1)
Neurological Issues
© Jennifer Bain, MD, PhD
23. Condition Percent of children (n)
Seizures 19% (6)
Grand mal 3% (1)
Infantile spasms 3% (1)
Petit mal 3% (1)
Complex partial 3% (1)
Simple partial 3% (1)
Febrile seizures 3% (1)
Seizure History
Age of onset: 1-3 years old
Effective medications endorsed
by 2 families:
• Keppra
• Phenobarbital
50% (3) of children have had
their seizures resolve
© Jennifer Bain, MD, PhD
24. Condition Percent of children (n)
Gastric reflux (heartburn) 55% (17)
Constipation 39% (12)
Diarrhea 10% (3)
Other (not specified) 6% (2)
Gastrointestinal Issues
© Jennifer Bain, MD, PhD
25. Condition Percent of children (n)
Otitis media (middle ear infections) 52% (16)
Requiring ear tubes 10% (3)
Pneumonia 13% (4)
Recurrent pneumonia 6% (2)
Urinary tract infection 3% (1)
Infections
© Jennifer Bain, MD, PhD
27. Condition Percent of children (n)
Kidney stones 3% (1)
Undescended testicles 3% (1)
Kidney, Urinary and Genital Issues
© Jennifer Bain, MD, PhD
28. Condition Percent of children (n)
Failure to thrive (difficulty
growing/gaining weight) 35% (11)
Short stature 6% (2)
Hypothyroidism
(underactive thyroid) 6% (2)
Hyperthyroidism
(overactive thyroid) 3% (1)
Diabetes 3% (1)
Growth and Hormone Issues
© Jennifer Bain, MD, PhD
29. Condition Percent of children (n)
Scoliosis (curvature of spine) 10% (3)
Pectus excavatum (caved in chest) 10% (3)
Hip dysplasia (partially or fully
dislocated hip joint) 6% (2)
Pectus carinatum (“pigeon chest”) 3% (1)
Bone Abnormalities
© Jennifer Bain, MD, PhD
30. Condition
High pain tolerance
Dental issues
Vascular problems
Sleep issues
Autonomic signs
New medical history questions
implemented this year
Percentages & numbers of children in the GRIN2B population with
these conditions will be reported at the next meeting
© Jennifer Bain, MD, PhD
31. Condition Percent of children (n)
Feeding tube 19% (6)
ENT
(i.e., ear tubes, adenoidectomy, and/or tonsillectomy) 16% (5)
Broken bone 13% (4)
Eye 6% (2)
Surgeries
© Jennifer Bain, MD, PhD
32. Condition Percent of children (n)
Gastrointestinal 31% (8)
Allergies/asthma 23% (6)
Sleep 15% (4)
Mood & behavior†
15% (4)
Seizures 8% (2)
Diabetes 4% (1)
Baclofen for dyskinesia 4% (1)
Current Medication Use
26 Individuals
† includes cannabidiol
© Jennifer Bain, MD, PhD
33. • 73% of kids are taking at
least 1 prescribed medication
• Of those taking more than 1
prescribed medication, most
are related to gastrointestinal
problems
• Additionally, 50% of
participants are taking at
least 1 vitamin or supplement
(not represented in the
graph)
• 31% are taking 2 or
more supplements
Current Medication Use
26 Individuals
© Jennifer Bain, MD, PhD
34. Summary of GRIN2B
Common issues Less common or
less serious issues• Vision/eye problems
• Seizures
• Growth - failure to thrive
• Neurological – clumsy,
low tone
• Developmental delay
• Autism spectrum
disorders
• Low muscle tone
• GI issues
• Ear and other infections
• Attention
deficit/hyperactivity disorder
© Jennifer Bain, MD, PhD
35. For researchers: how to access SFARI Base
https://base.sfari.org
• Create a SFARI Base Account
• Create a Project with your IRB Approval and
register your institution
• Sign a Researcher Distribution Agreement
and joinder
• Create a request for data or biospecimens
• Request will be reviewed by the SFARI science
team, and if approved, access to data is granted
© Jennifer Bain, MD, PhD