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 pathogenic variant 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 pathogenic variant found in NCL3. In addition, other multiple exon deletions are occasionally seen.
If the type of NCL is unknown a gene panel based analysis of all above-mentioned genes can be performed using NGS.
| 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 |
Detection rate:
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
Website links:
Sending patient material
Laboratory turnaround times
Databases / links: