APPLICATION OF CHROMOSOME-16 MARKERS IN THE DIFFERENTIAL-DIAGNOSIS OFNEURONAL CEROID-LIPOFUSCINOSIS

Accurate diagnosis of neuronal ceroid lipofuscinosis (NCL) is importan t for a correct prognosis of the disease and for genetic counseling, U p to now, no direct diagnostic test has been available for NCL, The cl inical diagnosis is made on the basis of symptoms, neurophysiological, neuroradiological, and specific lipopigment pattern data. Recent adva nces in the genetics of NCL have enabled us to use polymorphic DNA mar kers linked to the CLN1 and CLN3 loci as a tool in the differential di agnosis of NCL. We have applied genetic analysis with polymorphic DNA markers flanking the CLN3 gene on chromosome 16 to two consanguineous families in which NCL occurs, In the first family, which is of Turkish extraction, two patients suffering from a protracted form of juvenile NCL previously had been diagnosed with juvenile NCL, Haplotypes from this family indicate that the patients and their healthy sibling are h aplo-identical, suggesting that this protracted form of juvenile NCL i s not linked to the CLN3 locus, In the second family, which is of Moro ccan origin, one patient suffers from the early juvenile variant of NC L (Lake-Cavanagh), In this family, the patient and one of the healthy siblings have identical haplotypes, excluding linkage of early juvenil e NCL to the CLN3 locus on 16p12.1-11.2. Therefore, these cases from d ifferent populations demonstrate that haplotype analysis can be used a s an additional method to exclude the diagnosis of juvenile NCL. (C) 1 995 Wiley-Liss, Inc.