Title
A novel **POL** gene mutation in 4 children with alpers-like hepatocerebral syndromes A novel **POL** gene mutation in 4 children with alpers-like hepatocerebral syndromes
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Chicago, Ill. ,
Subject
Human medicine
Source (journal)
Archives of neurology / American Medical Association. - Chicago, Ill., 1960 - 2012
Volume/pages
67(2010) :2 , p. 239-244
ISSN
0003-9942
1538-3687
ISI
000274374600016
Carrier
E
Target language
English (eng)
Affiliation
University of Antwerp
Abstract
Objective: To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that, in association with 2 previously described mutations, caused an Alpers-like hepatocerebral syndrome in 4 children. Design: Genotype-phenotype correlation. Setting: Tertiary care universities. Patients: Four children, 2 related and 2 unrelated, with the novel p.P1073L mutation (all patients) and either the p.A467T (2 patients), p.G848S (1 patient), or p.W748S (1 patient) mutation presented with psychomotor delay, encephalopathy, and liver failure. Interventions: Detailed clinical and laboratory examinations including brain magnetic resonance imaging, muscle biopsy, measurement of mitochondrial DNA, and sequencing of the POLG gene. Main Outcome Measures: Definition of clinical variability. Results: All 4 patients had psychomotor delay, seizures, and liver disease. Three patients had severe gastrointestinal dysmotility, which may be associated with the new p.P1073L mutation. Conclusions: The heterozygous presence of the novel p.P1073L mutation in trans with another recessive POLG mutation causes a hepatocerebral disorder identical or very similar to Alpers syndrome. This adds to the already striking clinical heterogeneity of POLG mutations. In the Belgian patients, the familial occurrence without consanguinity is related to the high frequency of the recessive p.A467T and p.W748S mutations in northwestern Europe and reveals a pitfall for diagnosis and genetic counseling.
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