Zhong Nanbert, Ju Weina, Moroziewicz Dorota, Wronska Anetta, Li Marilyn, Wisniewski Krystyna, Brooks Susan Sklower, Jenkins Edmund, Brown W Ted
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Beijing Da Xue Xue Bao Yi Xue Ban. 2005 Feb 18;37(1):20-5.
Infantile (INCL, NCL1) and late-infantile (LINCL, NCL2) neuronal ceroid lipofuscinoses have been found to result from genetic deficiency of genes CLN(1 ) and CLN(2), respectively. The application of molecular analyses can facilitate prenatal diagnosis for families affected by NCL1 or NCL2, in which the familial mutation(s) have been identified. Molecular testing with allele-specific primer extension and DNA sequencing was performed in nine pregnancies, four from two NCL1 families and five from five NCL2 families. Lysosomal enzyme activity assays were carried out as well.Four fetuses from three pregnancies in NCL1 families were found to be carriers for a mutation 451C-T in the CLN(1) gene and one was normal. Prenatal testing of three NCL2 families who carried mutation R208X in the CLN(2) gene showed that all fetuses were carriers. In NCL2 families who carried either mutation IVS5-1C or/and IVS5-1A two normal pregnancies were detected. Our studies indicate that DNA testing, which may provide definitive prenatal diagnosis for NCL, may be used in combination with lysosomal enzyme activity analyses.
婴儿型（INCL，NCL1）和晚婴儿型（LINCL，NCL2）神经元蜡样脂褐质沉积症已被发现分别是由CLN(1)和CLN(2)基因的遗传缺陷所致。分子分析的应用有助于对受NCL1或NCL2影响的家庭进行产前诊断，其中家族性突变已被确定。对9例妊娠进行了等位基因特异性引物延伸和DNA测序的分子检测，其中4例来自两个NCL1家族，5例来自五个NCL2家族。同时进行了溶酶体酶活性测定。在NCL1家族的3例妊娠中，4例胎儿被发现是CLN(1)基因451C-T突变的携带者，1例正常。对携带CLN(2)基因R208X突变的3个NCL2家族进行产前检测，结果显示所有胎儿均为携带者。在携带IVS5-1C或/和IVS5-1A突变的NCL2家族中，检测到2例正常妊娠。我们的研究表明，可提供NCL确定性产前诊断的DNA检测可与溶酶体酶活性分析联合使用。
