J. lnher. Metab. Dis. 19 (1996) 269-274 © SSIEMand KluwerAcademicPublishers. Printed in the Netherlands Annotation Recent advances in the molecular genetics of the neuronal ceroid lipofuscinoses S. E. MOLE Universily College London, Department of Pediatrics, The Rayne Institute, Universi O, Street, London WC1E 6J J, UK Summary: Major advances in the molecular genetic analysis of the neuronal ceroid lipofuscinoses (NCL) have recently been made: the genes for two major types have been identified and the chromosomal location for a third defined. CLN1, the gene for infantile NCL (Santavuori-Haltia disease) encodes palmitoyl protein thioesterase (PPT). Most patients (75% of disease chromosomes) have the same point mutation. In contrast, CLN3, the gene for juvenile NCL (Batten or Spielmeyer-Vogt-Sj6gren disease) is not a previously known gene, nor does its product display homology to any previously described proteins. The same 1 kb genomic deletion is present in the majority of patients (81% of disease chromosomes). CLNS, the gene for Finnish variant late infantile NCL, has been mapped to 13q and should be identified in the near future. The gene for late-infantile NCL (Jansky-Bietschowsky disease) has not yet been localized to a chromosome despite intensive research. It is likely that this type of NCL is caused by mutations in more than one gene each resulting in the same phenotype. The neuronal ceroid lipofuscinoses (NCL) are the most common of the neurodegenerative disorders of childhood and, although rare, have a devastating effect on families. At the present time there is no known treatment which prevents or delays onset and progression of the disease. The NCLs comprise a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment (ceroid and lipofuscin) in many tissues. The main clinical features are failure of psychomotor development, impaired vision, seizures and premature death (Santavuori 1988). Three main childhood types are recognized on the basis of age of onset, clinical phenotype, and ultrastructural characterization and content of the storage material. Inheritance of all childhood types is autosomal recessive. These, with their eponyms, include: infantile (Santavuori-Haltia disease, INCL; CLN1), late-infantile (Jansky-Bielschowsky disease, LtNCL; CLN2) and juvenile (Batten or Spietmeyer-Vbgt-Sj6gren disease, JNCL; CLN3) NCL. Rare, variant types with clinical phenotypes which fall in between the three main types are now also recognized. These include Finnish variant late-infantile (Finnish variant Jansky- Bielschowsky disease, CLNS), and early-onset juvenile with granular osmiophilic deposits (no locus assigned). An adult type has also been reported (Kufs or Parry disease, CLN4). 269