DNA DIAGNOSIS AND IDENTIFICATION OF CARRIERS OF INFANTILE AND JUVENILE NEURONAL CEROID-LIPOFUSCINOSES

The recent identification of the genes and the mutations underlying in fantile neuronal ceroid lipofuscinosis and juvenile onset neuronal cer oid lipofuscinosis facilitates specific DNA-based diagnostics for the disorders. We have developed a solid-phase minisequencing test for the identification of the major Finnish INCL mutation, an A to T transver sion at nucleotide position 364 of the palmitoyl protein thioesterase gene on chromosome 1. This test has been applied for prenatal diagnosi s and for identification of disease carriers in INCL families. For pop ulation-based screening for INCL carriers the coverage of the test wou ld be 98%. In addition, by combining the solid-phase minisequencing te st with whole genome preamplification, we have developed a procedure t hat allows reliable identification of the INCLFin-mutation in single b lastomeres from in-vitro-fertilized embryos. This method is applicable for preimplantation diagnosis, and thus it offers an alternative to e arly prenatal diagnosis in the prevention of INCL, A modification of t he solid-phase minisequencing test was devised for detection of the ma jor JNCL mutation, a 1.02 kb deletion in the CLN3 gene on chromosome 1 6. The coverage of this test for diagnosis of JNCL and identification of carriers is 90% in Finland and > 80% worldwide.