Neuronal ceroid lipofuscinosis (NCL)

OMIM:  256730, 204500, 204200, 606725, 607837, 600143

Gene

Disease

PPT1 (CLN1)

NCL 1/Neuronal ceroid lipofuscinosis, infantile adult

TPP1 (CLN2)

NCL 2/Neuronal ceroid lipofuscinosis, late infantile (Jansky-Bielchowsky disease)

CLN3

NCL 3/Neuronal ceroid lipofuscinosis, juvenile (Batten-Spielmeyer-Vogt disease)

CLN6

NCL 6/Neuronal ceroid lipofuscinosis, late infantile (Kufs type)

CLN8

NCL 8/ laat infantiele Neuronale Ceroid Lipofuscinose (Turkish variant or Northern Northernepilepsie/ EPMR (progressive epilepsy with mental retardation)

Procedure:

Depending on the phenotype and laboratory findings (laboratory testing of the lysosomal enzymes palmitoyl protein thioesterase I or tripeptidyl-peptidase I), a specific mutation analysis (usually 3, 1 or 2) of the corresponding gene is requested for the index patient. Mutation analysis of CLN6 and 8 is usually only carried out when no mutation was found in other genes. If two mutations are found, carrier testing can be offered to parents and other family members. Prenatal testing can also be provided as needed.

NB: a deletion of exons 7+8 (1 kb deletion) is the most common mutation found in NCL 3. In addition, other multiple exon deletions are occasionally seen.

Detection ratio:
NCL 1: 58% (n=19)
NCL 2: 58% (n=36)
NCL 3: 37% (n=98) Note: In 2 patients only one mutation was detected.
NCL 6 and NCL 8: insufficient data available

Gene

Techniques

PPT1 (CLN1)

Sequence analysis of the entire coding region (exons 1 to 9), including the intron/exon junctions

TPP1 (CLN2)

Sequence analysis of the entire coding region (exons 1 to 13), including intron/exon junctions

CLN3

PCR of the 1 kb deletion (exons 7+8), and sequence analysis of the entire coding region (exons 1 to 15) including intron/exon junctions

CLN6

Sequence analysis of virtually the entire coding region (exons 2 to 7), including intron/exon junctions

CLN8

Sequence analysis of the entire coding region (exons 2 and 3), including intron/exon junctions

Please note: for all genes a MLPA test is available (MRC Holland P470)

 

Gene

Gene product

Locus

Inheritance

OMIM number

Reference Sequence

PPT1 (CLN1)

PPT1

1p32

Autosomal recessive

# 256730

NM_000310.3

TPP1 (CLN2)

TPP1

11p15.5

Autosomal recessive

#204500

NM_000391.3

CLN3

 

16p12.1

Autosomal recessive

# 204200

NC_000016.9; NM_001042432.1

CLN6

 

15q21-q23

Autosomal recessive

# 606725

NT_010194.16; NM_017882.2

CLN8

Mitochondrial ATP synthase subunit C

8p23

Autosomal recessive

#607837, 600143

NT_023736.15; NM_O18941.3

Website links:

Sending patient material

Laboratory turnaround times 

Databases / links:

www.ucl.ac.uk/ncl/