Positional candidate gene cloning of CLN1

Advances in Genetics
S L HofmannA A Soyombo

Abstract

Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (PPT) underlie the recessive neurodegenerative disorder, infantile Batten disease, or infantile neuronal ceroid lipofuscinosis (INCL). The CLN1 gene was mapped to chromosome 1p32 in the vicinity of a microsatellite marker HY-TM1 in a cohort of Finnish INCL families, and mapping of the PPT gene to the CLN1 critical region (and the discovery of mutations in PPT in several unrelated families) led to conclusive identification of PPT as the disease gene. PPT is a lysosomal thioesterase that removes fatty acids from fatty-acylated cysteine residues in proteins. The accumulation of fatty acyl cysteine thioesters can be reversed in INCL cells by the exogenous administration of recombinant PPT, which enters the cells through the mannose 6-phosphate receptor pathway. Over two dozen PPT mutations have been found in PPT-deficient patients worldwide. In the United States, all PPT-deficient patients show "GROD" histology but the age of onset of symptoms is later in some children due to the presence of missense mutations that result in enzymes with residual PPT activity. Now that INCL is known to be caused by a defect in a soluble lysosomal enzyme, appropriate therapies may be...Continue Reading

Citations

Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·P GuptaS L Hofmann
Nov 1, 2007·Expert Opinion on Medical Diagnostics·Amanda L GettyDavid A Pearce
Dec 2, 2020·International Journal of Molecular Sciences·Akiko SuzukiJunichi Iwata
Oct 30, 2020·Journal of Neuroinflammation·Kristina BerveJanos Groh

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Batten Disease

Batten Disease is a group of nervous system disorders known as neuronal ceroid lipofuscinosis. This feed focuses on neurobiological and neuropathological aspects of this disease.