Linked Life Data

19021637

Source:http://linkedlifedata.com/resource/pubmed/id/19021637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-1-8
pubmed:abstractText
Metachromatic leukodystrophy (MLD), a severe neurodegenerative metabolic disorder, is caused by deficient activity of arylsulfatase A (ARSA; EC 3.1.6.8), which leads to a progressive demyelinating process in central and peripheral nervous systems. In this study, a DNA sequence analysis was performed on six Polish patients with different types of MLD. Six novel mutations were identified: one nonsense (p.R114X), three missense (p.G122C, p.G293C, p.C493F) and two frameshift mutations (g.445_446dupG and g.2590_2591dupC). Substitutions p.G293C and p.C493F and duplication g.445_446dupG caused a severe reduction of enzyme activity in transient transfection experiments on mammalian cells (less than 1% of wild-type (WT) ARSA activity). Duplication 2590_2591dupC preserved low-residual ARSA activity (10% of WT ARSA). In summary, the novel MLD-causing mutations in the exons 2, 5 and even in 8 of the ARSA gene described here can be classified as severe type 0, leading in homozygosity to the late infantile form MLD. Growth retardation, delayed motor development, gait disturbances, tonic-clonic seizures and non-epileptic muscle spasms were the first onset symptoms in patients with late infantile form of MLD. In individual with juvenile type MLD gait disturbances evidenced the onset of the disease, while in a patient with late juvenile MLD, difficulties at school were displayed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1399-0004
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-64
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Molecular and clinical consequences of novel mutations in the arylsulfatase A gene.
pubmed:affiliation
Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't