A rapid fluorogenic palmitoyl-protein thioesterase assay: Pre- and postnatal diagnosis of INCL

被引：94

作者：

van Diggelen, OP

Keulemans, JLM

Winchester, B

Hofman, IL

Vanhanen, SL

Santavuori, P

Voznyi, YV

机构：

[1] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands

[2] Inst Child Hlth, London, England

[3] Bartimeushage, Doorn, Netherlands

[4] Hosp Children & Adolescents, Dept Paediat Neurol, Helsinki, Finland

[5] Inst Organ Chem, Moscow, Russia

来源：

MOLECULAR GENETICS AND METABOLISM | 1999年 / 66卷 / 04期

关键词：

infantile neuronal ceroid lipofuscinosis; INCL; CLN1; palmitoyl-protein thioesterase; PPT1; enzyme analysis; prenatal diagnosis;

D O I：

10.1006/mgme.1999.2809

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

A deficiency of palmitoyl-protein thioesterase (PPT) was recently shown to be the primary defect in infantile neuronal ceroid lipofuscinosis (INCL). The available enzyme assays are complicated and impractical for diagnostic use. We have recently developed a new, fluorometric assay for PPT based on the sensitive fluorochrome 4-methylumbelliferone, requiring an overnight incubation to measure PPT, Now we have synthesized an analogue of this substrate which allows PPT determinations in 1 h. This improved PPT assay is simple, sensitive, and robust and will. facilitate the definition of the full clinical spectrum associated with a deficiency of PPT. PPT activity was readily detectable in fibroblasts, leukocytes, amniotic fluid cells, chorionic villi, plasma, and cerebrospinal fluid from controls. PPT activity was profoundly deficient in these tissues and fluids from INCL patients. Similarly, a deficiency of PPT activity was demonstrated in patients with the variant juvenile NCL with GROD. These results show the feasibility of rapid pre- and postnatal diagnosis of INCL and its variants. (C) 1999 Academic Press.

引用

页码：240 / 244

页数：5

共 13 条

[1] Atypical juvenile neuronal ceroid liposfuscinosis with granular osmiophilic deposit-like inclusions in the autonomic nerve cells of the gut wall [J].

Åberg, L ;

Järvelä, I ;

Rapola, J ;

Autti, T ;

Kirveskari, E ;

Lappi, M ;

Sipilä, L ;

Santavuori, P .

ACTA NEUROPATHOLOGICA, 1998, 95 (03) :306-312

[2]

CAMP LA, 1993, J BIOL CHEM, V268, P22566

[3]

Cho SG, 1998, J NEUROCHEM, V71, P323

[4] 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

[5] THE NEURONAL CEROID-LIPOFUSCINOSES [J].

GOEBEL, HH .

JOURNAL OF CHILD NEUROLOGY, 1995, 10 (06) :424-437

[6] Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease [J].

Järvelä, I ;

Sainio, M ;

Rantamäki, T ;

Olkkonen, VM ;

Carpén, O ;

Peltonen, L ;

Jalanko, A .

HUMAN MOLECULAR GENETICS, 1998, 7 (01) :85-90

[7] 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

[8]

Penefsky H S, 1979, Methods Enzymol, V56, P527

[9] Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis [J].

Sleat, DE ;

Donnelly, RJ ;

Lackland, H ;

Liu, CG ;

Sohar, I ;

Pullarkat, RK ;

Lobel, P .

SCIENCE, 1997, 277 (5333) :1802-1805

[10] A FLUORIMETRIC ENZYME ASSAY FOR THE DIAGNOSIS OF MORQUIO-DISEASE TYPE-A (MPS-IV-A) [J].

VANDIGGELEN, OP ;

ZHAO, H ;

KLEIJER, WJ ;

JANSE, HC ;

POORTHUIS, BJHM ;

VANPELT, J ;

KAMERLING, JP ;

GALJAARD, H .

CLINICA CHIMICA ACTA, 1990, 187 (02) :131-139

← 1 2 →