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Titolo:
MOLECULAR-GENETICS OF PALMITOYL PROTEIN THIOESTERASE DEFICIENCY IN THE US
Autore:
DAS AK; BECERRA CHR; YI W; LU JY; SIAKOTOS AN; WISNIEWSKI KE; HOFMANN SL;
Indirizzi:
UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES,5323 HARRY HINES BLVD DALLAS TX 75235 UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES DALLAS TX 75235 UNIV TEXAS,SW MED CTR,DEPT INTERNAL MED DALLAS TX 75235 INDIANA UNIV,SCH MED,DEPT PATHOL INDIANAPOLIS IN 46202 NEW YORK STATE INST BASIC RES DEV DISABIL,DEPT PATHOL NEUROBIOL STATEN ISL NY 10314 SUNY HLTH SCI CTR BROOKLYN NY 11203
Titolo Testata:
The Journal of clinical investigation
fascicolo: 2, volume: 102, anno: 1998,
pagine: 361 - 370
SICI:
0021-9738(1998)102:2<361:MOPPTD>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURONAL CEROID-LIPOFUSCINOSIS; MUTATIONS; CLONING; ENZYME;
Keywords:
LYSOSOMAL STORAGE DISORDERS; THIOLESTER HYDROLASES; NEURONAL CEROID LIPOFUSCINOSIS; METABOLIC BRAIN DISEASES; MOLECULAR GENETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
A.K. Das et al., "MOLECULAR-GENETICS OF PALMITOYL PROTEIN THIOESTERASE DEFICIENCY IN THE US", The Journal of clinical investigation, 102(2), 1998, pp. 361-370

Abstract

Mutations in a newly described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), were recently shown to be responsible for an autosomal recessive neurological disorder prevalent in Finland, infantile neuronal ceroid lipofuscinosis. The disease results in blindness, motor and cognitive deterioration, and seizures. Characteristic inclusion bodies (granular osmiophilic deposits [GROD]) are found in the brain and other tissues. The vast majority of Finnish cases are homozygous for amissense mutation (R122W) that severely affects PPT enzyme activity, and the clinical course in Finnish children is uniformly rapidly progressive and fatal. To define the clinical, biochemical; and molecular genetic characteristics of subjects with PPT deficiency in a broader population, we collected blood samples from U.S. and Canadian subjects representing 32 unrelated families with neuronal ceroid lipofuscinosis who had GROD documented morphologically. We measured PPT activity and screened the coding region of the PPT gene for mutations. In 29 of thefamilies, PPT deficiency was found to be responsible for the neurodegenerative disorder, and mutations were identified in 57 out of 58 PPT alleles. One nonsense mutation (R151X) accounted for 40% of the alleles and was associated with severe disease in the homozygous state. A second mutation (T75P) accounted for 13% of the alleles and was associated with a late onset and protracted clinical course. A total of 19 different mutations were found, resulting in a broader spectrum of clinical presentations than previously seen in the Finnish population. Symptoms first appeared at ages ranging from 3 mo to 9 yr, and about half of the subjects have survived into the second or even third decades of life.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 16:54:11