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The document discusses variants in the GRIN2A and GRIN2B genes. It summarizes findings from studies that analyzed 247 cases with GRIN2A variants and 91 cases with GRIN2B variants. The clinical features and severity of phenotypes associated with variants in these genes and other GRIN genes are compared. The presentation concludes by proposing the creation of a single large shared database for GRIN variants that would be accessible to researchers.

Gesundheitswesen

Clinical and genetic spectrum
of GRIN2A and GRIN2B variants
Johannes Lemke
Atlanta
13.09.2019
© Johannes Lemke

2
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

3
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
Konrad Platzer
Vincent Strehlow
Henrike Heyne
Rami Jamra
Team in Leipzig
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

4
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
www.grin-database.de
>100x GRIN1
>250x GRIN2A
>100x GRIN2B
few GRIN2D
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta; www.grin-database.de © Johannes Lemke

5
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
www.grin-database.de
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta; www.grin-database.de © Johannes Lemke

6
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
247 cases with GRIN2A
(Strehlow et al., 2019)
Some variants are unique, some are recurrent
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

7
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
247 cases with GRIN2A
(Strehlow et al., 2019)
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

8
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
247 cases with GRIN2A
(Strehlow et al., 2019)
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

9
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
247 cases with GRIN2A
(Strehlow et al., 2019)
LBD
Membrane
M1
ABD
ATD
M4
M2
M3
This situation is
a bit more
complex…
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

10
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
91 cases with GRIN2B
(Platzer et al., 2017)
GRIN2A
GRIN2B
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

11
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
91 cases with GRIN2B
(Platzer et al., 2017)
Intellectual disability
GRIN1 5% mild 95% profound
GRIN2A 38% normal 20% mild 23% mod-prof
GRIN2B 15% mild 85% mod-prof
GRIN2D 100% profound
Impaired speech
GRIN1 100%
GRIN2A 92%
GRIN2B 100%
GRIN2D 100%
seizures
GRIN1 70% (9% ES)
GRIN2A 88% (2% ES, 55% focal, 10% generalized)
GRIN2B 52% (37% ES)
GRIN2D 100% (100% ES)
Movement disorders
GRIN1 61% (22% OGC)
GRIN2A <10%
GRIN2B 10%
GRIN2D 100%
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

12
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
91 cases with GRIN2B
(Platzer et al., 2017)
MRI findings
GRIN1 58% cortical atrophy some MCD
GRIN2A Rarely cortical atrophy
GRIN2B 9% cortical atrophy 14% MCD
GRIN2D 100% cortical atrophy
Muscular hypotonia
GRIN1 71%
GRIN2A rare
GRIN2B 53%
GRIN2D 100%
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

13
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
91 cases with GRIN2B
(Platzer et al., 2017)
Polymicrogyria + large, dysplastic basal ganglia
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

14
Leipzig
GRIN-DB
GRIN2A
GRIN2B
Outlook
What should we aim for?
ONE big
shared DB
Organised
by any
initiative
Content
revised by
researchers
Accessable
by
researchers
Johannes Lemke, 13.09.2019, CFERV Conference on GRIN variants, Atlanta © Johannes Lemke

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