Molecular diagnosis of and carrier screening for the neuronal ceroid lipofuscinoses

被引:10
作者
Zhong, NA
Wisniewski, KE
Ju, WN
Moroziewicz, DN
Jurkiewicz, A
McLendon, L
Jenkins, EC
Brown, WT
机构
[1] New York State Inst Basic Res Dev Disabil, Mol Neurogenet Diagnost Lab, Staten Isl, NY 10314 USA
[2] New York State Inst Basic Res Dev Disabil, Specialty Clin Labs, Staten Isl, NY 10314 USA
[3] New York State Inst Basic Res Dev Disabil, Dept Human Genet, Staten Isl, NY 10314 USA
[4] New York State Inst Basic Res Dev Disabil, Dept Pathol Neurobiol, Staten Isl, NY 10314 USA
[5] SUNY Hlth Sci Ctr, Dept Neurol, Brooklyn, NY 11203 USA
来源
GENETIC TESTING | 2000年 / 4卷 / 03期
关键词
D O I
10.1089/10906570050501452
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The neuronal ceroid lipofuscinoses (NCLs) are a large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction, Three typical forms, the infantile (INCL), late-infantile (LINCL), and juvenile (JNCL), are among the most common childhood-onset neurodegenerative disorders. They result from mutations on genes CLN1, CLN2, and CLN3, respectively. We determined that the mutations 223A --> G and 451C --> T in CLN1, T523-1G --> C, and 636 C --> T in CLN2, and deletion of a 1.02-kb genomic fragment in CLN3 are the five common mutations for NCL, To offer clinical genetic testing for the NCLs, we have developed simple and quick PCR-based molecular tests for detecting INCL-, LINCL-, and JNCL-affected individuals from 180 NCL families (27 INCL, 76 LINCL, and 77 JNCL), The sensitivity of testing to detect NCL patients among clinically suspected individuals was determined to be 78% (21/27) for INCL, 66% (54/76) for LINCL, and 75% (58/77) for JNCL, When molecular screening for carriers was conducted among the normal siblings or parents of the probands, we identified two carriers out of three individuals tested for INCL, 20/56 (35.7%) carriers for LINCL, and 48/106 (45.3 %) carriers for JNCL families. In addition, 5% (9/180) of NCL patients revealed genetic heterogeneity and were reclassified. Seven patients previously diagnosed as having JNCL were now found to carry mutations of CLN2 (5/7) or CLN1 (2/7) and 2 with late-infantile onsets were identified as carrying mutations of CLN1. Our data demonstrate the importance of DNA testing to detect accurately both affected individuals and carriers in NCL families.
引用
收藏
页码:243 / 248
页数:6
相关论文
共 25 条
[1]   The neuronal ceroid-lipofuscinoses (Batten disease): A new class of lysosomal storage diseases [J].
Bennett, MJ ;
Hofmann, SL .
JOURNAL OF INHERITED METABOLIC DISEASE, 1999, 22 (04) :535-544
[2]   Molecular genetics of palmitoyl protein thioesterase deficiency in the US [J].
Das, AK ;
Becerra, CHR ;
Yi, W ;
Lu, JY ;
Siakotos, AN ;
Wisniewski, KE ;
Hofmann, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (02) :361-370
[3]  
EIBERG H, 1989, CLIN GENET, V36, P217
[4]   Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene [J].
Hartikainen, JM ;
Ju, WN ;
Wisniewski, KE ;
Moroziewicz, DN ;
Kaczmarski, AL ;
McLendon, L ;
Zhong, D ;
Suarez, CT ;
Brown, WT ;
Zhong, N .
MOLECULAR GENETICS AND METABOLISM, 1999, 67 (02) :162-168
[5]   INFANTILE FORM OF NEURONAL CEROID LIPOFUSCINOSIS (CLN1) MAPS TO THE SHORT ARM OF CHROMOSOME-1 [J].
JARVELA, I ;
SCHLEUTKER, J ;
HAATAJA, L ;
SANTAVUORI, P ;
PUHAKKA, L ;
MANNINEN, T ;
PALOTIE, A ;
SANDKUIJL, LA ;
RENLUND, M ;
WHITE, R ;
AULA, P ;
PELTONEN, L .
GENOMICS, 1991, 9 (01) :170-173
[6]   ISOLATION OF A NOVEL GENE UNDERLYING BATTEN-DISEASE, CLN3 [J].
LERNER, TJ ;
BOUSTANY, RMN ;
ANDERSON, JW ;
DARIGO, KL ;
SCHLUMPF, K ;
BUCKLER, AJ ;
GUSELLA, JF ;
HAINES, JL ;
KREMMIDIOTIS, G ;
LENSINK, IL ;
SUTHERLAND, GR ;
CALLEN, DF ;
TASCHNER, PEM ;
DEVOS, N ;
VANOMMEN, GJB ;
BREUNING, MH ;
DOGGETT, NA ;
MEINCKE, LJ ;
LIU, ZY ;
GOODWIN, LA ;
TESMER, JG ;
MITCHISON, HM ;
ORAWE, AM ;
MUNROE, PB ;
JARVELA, IE ;
GARDINER, RM ;
MOLE, SE .
CELL, 1995, 82 (06) :949-957
[7]   Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits [J].
Mitchison, HM ;
Hofmann, SL ;
Becerra, CHR ;
Munroe, PB ;
Lake, BD ;
Crow, YJ ;
Stephenson, JBP ;
Williams, RE ;
Hofman, IL ;
Taschner, PEM ;
Martin, JJ ;
Philippart, M ;
Andermann, E ;
Andermann, F ;
Mole, SE ;
Gardiner, RM ;
O'Rawe, AM .
HUMAN MOLECULAR GENETICS, 1998, 7 (02) :291-297
[8]  
Mole SE, 1999, HUM MUTAT, V14, P199
[9]   Batten disease: Four genes and still counting [J].
Mole, SE .
NEUROBIOLOGY OF DISEASE, 1998, 5 (05) :287-303
[10]   Spectrum of mutations in the Batten disease gene, CLN3 [J].
Munroe, PB ;
Mitchison, HM ;
ORawe, AM ;
Anderson, JW ;
Boustany, RM ;
Lerner, TJ ;
Taschner, PEM ;
deVos, N ;
Breuning, MH ;
Gardiner, RM ;
Mole, SE .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (02) :310-316