TPP1

TPP1

A gene on chromosome 11p15 that encodes a sedolisin-type serine protease, which acts in lysosomes to cleave N-terminal tripeptides from substrates; it also has weak endopeptidase activity. Tripeptidyl peptidase I is activated and auto-proteolysed by acidification.

Molecular pathology
TPP1 mutations have been linked to late-infantile neuronal ceroid lipofuscinosis (CLN2, Jansky-Bielschowsky disease), which is due to the failure to degrade specific neuropeptides, and a subunit of ATP synthase in lysosomes.
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In most children with the late infantile form of Batten disease and the affected dogs, mutations in the TPP1 gene disable the body's ability to produce the enzyme tripeptidyl peptidase 1 (TPP1), which normally allows brain cells to recycle cellular waste.
Evaluation of the canine TPP1 gene as a candidate for neuronal ceroid lipofuscinosis in Tibetan terrier and Polish Owczarek Nizinny dogs.
To date, more than 30 mutations have been reported in the PPT1 and TPP1 genes, rendering molecular genetic analysis impractical as a primary means of diagnosis.
Enzymatic assays based on fluorescent substrates have recently been reported for PPT1 (2) and TPP1 (3).
In addition, heating of dried blood cards to 50 [degrees]C for 3 h, which inactivates enzymes in liquid EDTA-blood samples, did not affect TPP1 or PPT1 activities in DBS (data not shown).
In conclusion, this new method allows the rapid and accurate determination of PPT1 and TPP1 activities from dried blood samples and a clear differentiation between healthy individuals, patients with neuronal ceroid lipofuscinoses (CLN1 and CLN2), and heterozygous carriers.
Ultimately, the physicians turned to SV Bio, where the patient genomes were sequenced and the underlying genetic mutation in a gene named TPP1 was uncovered immediately.