Download Neuronal Ceroid-Lipofuscinosis type 3 (NCL3)

Version 5 (October 2012)
NE THAMES REGIONAL MOLECULAR GENETICS SERVICE
Neuronal Ceroid-Lipofuscinosis type 3 (NCL3)
(Juvenile Batten disease (JNCL))
Contact details
Molecular Genetics
GOSH NHS Trust
Level 6
York House
37 Queen Square
London
WC1N 3BH
Telephone
+44 (0) 20 7762 6888
Fax
+44 (0) 20 7813 8196
Introduction
Neuronal ceroid-lipofuscinosis type 3 (NCL3; MIM #204200) is a rare autosomal
recessive neurodegenerative disorder caused by mutations in the CLN3 gene. NCL3 is
one of at least eight genetically distinct diseases associated with the NCL disease
spectrum. NCL3 is generally referred to as juvenile NCL (JNCL) due typical onset of
symptoms between the ages of 4 and 7 years. A rare variant form of JNCL (vJNCL) has
been associated with mutations in the CLN1 gene (usually associated with the infantile
form of the disease).
NCL3 is typically characterised by normal development until the onset of visual failure
due to retinal degeneration between 4 and 7 yrs. Progression of visual loss is usually
rapid. Other clinical features include seizures and psychomotor deterioration; prognosis
is poor. The differential diagnosis of NCL3 from the other NCL types is based on age of
onset, clinical phenotype and ultra structural characterisation of the storage material.
NCL3 is characterised by the accumulation of auto fluorescent lipopigment with a
fingerprint profile in neurones and other cell types and the presence of vacuolated
lymphocytes on a blood smear.
The CLN3 gene (16p12) consists of 15 exons spanning 15kb of genomic DNA. A
1.02kb deletion (introns 6-8) is reported to account for ~69% of JNCL alleles (~85% in
Finnish population). Other disease causing mutations are family specific and found
throughout the gene.
Samples required
5ml venous blood in
plastic EDTA bottles
(>1ml from neonates)
Prenatals must be
arranged in advance,
through a Clinical
Genetics department if
possible. Amniotic
fluid or CV samples
should be sent to
Cytogenetics for
dissecting and
culturing, with
instructions to forward
the sample to the
Regional Molecular
Genetics laboratory for
analysis
A completed DNA
request card should
accompany all
samples.
Referrals

Clinical and histopathological review of the affected patient is recommended to
indicate a diagnosis of NCL3. Please supply details of biochemical and
histopathological testing undertaken, clinical details and any relevant
pedigree. If the necessary patient samples are unavailable genetic testing can
be undertaken in the parents of an affected child.

Carrier testing can be offered to the adult relatives of NCL3 patients once a
disease causing mutation has been identified.
Prenatal testing
Prenatal testing is available for families in which the diagnosis of NCL3 has been
confirmed by mutation analysis. Please contact the laboratory to discuss.
Service offered
Level 1: Testing for the common 1.02kb deletion.
Level 2: Screening of the CLN3 gene by direct sequence analysis.
Target reporting time
2 weeks for routine 1.02kb deletion mutation test in the index case.
8 weeks for sequence analysis of the gene in the index case.
2 weeks for family member carrier testing.
For urgent samples please contact the laboratory.
Contact details for histopathology laboratory:
Histopathology, Level 3, Camelia Botnar Laboratories, Great Ormond Street Hospital,
London WC1N 3JH.
Tel: +44 (0) 20 7405 9200 (x7907)
Patient details
To facilitate accurate testing and reporting please provide patient demographic details (full name, date of birth,
address and ethnic origin), details of any relevant family history and full contact details for the referring clinician