The Adult NCL Gene Discovery Consortium*
In comparison to the childhood onset
NCLs our understanding of the adult onset
forms is limited. The Consortium aims to
change this through gene discovery.
Adult NCL is more difficult to diagnose
than childhood forms as it is rare, not well
studied and pathological diagnosis is
STEP 1: Is Adult NCL the correct
Based on the literature, we established
formal criteria for diagnosis of Adult NCL.
Clinical and pathological data are reviewed
in detail by experts in the Consortium.
The outcome of this review sees each
patient classified according to the certainty
of their diagnosis (i.e., Definite, Probable,
Possible, or Not Adult NCL).
STEP 2: Gene Discovery efforts
What results do we have so far?
Data on 49 putative Adult NCL patients
has been collated to date. The formal
Figure: Formal review process for Consortium patients
with a diagnosis of Adult NCL.
Adult NCL patients review process is complete for thirty-one.
referred to Consortium
members for genetic
Importantly, 70% of cases classified so far
as ‘Not Adult NCL’ (n=22):
• Misdiagnosed with Kufs (n=17)
• Inadequate review material (n=5)
Single ‘Definite’ case subsequently tested
positive for CLN6 mutations (known gene)
What do these preliminary results tell us?
Diagnosing Adult NCL is tough!
Of the 49 cases studied, it is likely that
only a small subset will meet the criteria
for gene discovery efforts.
What future benefits might this research
lead to for the patient?
• It will simplify the diagnostic process,
requiring only a simple DNA sample.
• There will be a greater understanding of
the clinical and pathological features,
including disease progression/prognosis.
• Family members will be able to be tested
for their genetic risk.
• Opportunity for developing new treatment
options will be created.
Overall Patient Classification
according to Consortium consensus
(n = 31 to date)
Gene discovery efforts
Using Next-Generation Sequencing, all
~20,000 human genes will be searched for
mistakes (or mutations) in the DNA
sequence of each ‘Definite’, ‘Probable’ or
‘Possible’ Adult NCL disease case.
* Adult NCL Consortium Members – The University of Melbourne: Samuel F Berkovic, Karen L Oliver, Katherine R Smith, Michael Hildebrand, John Damiano, Melanie
Bahlo – Charles University in Prague: Stanislav Kmoch – University College London: Sara Mole, Glen Anderson – Harvard University in Boston: John Staropoli,
Katherine Sims, Susan Cotman – Université de Montréal: Patrick Cossette, Maxime Dion-Caudieux – Hospital São João in Porto: Stirling Carpenter