title: Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy.
abstract: Autosomal recessive progressive external ophthalmoplegia (PEO) is one clinical disorder associated with multiple mitochondrial DNA deletions and can be caused by missense mutations in POLG, the gene encoding the mitochondrial DNA polymerase gamma. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is another autosomal recessive disorder associated with PEO and multiple deletions of mitochondrial DNA in skeletal muscle. In several patients this disorder is caused by loss of function mutations in the gene encoding thymidine phosphorylase (TP). We report a recessive family with features of MNGIE but no leukoencephalopathy in which two patients carry three missense mutations in POLG, of which two are novel mutations (N846S and P587L). The third mutation was previously reported as a recessive POLG mutation (T251I). This finding indicates the need for POLG sequencing in patients with features of MNGIE without TP mutations.
authors.affiliation: Neuromuscular Reference Center and Department of Neurology, University Hospital of Antwerp (UZA), Antwerpen, Belgium. vgoethge@uia.ua.ac.be
authors.forename: Gert
authors.initials: G
authors.lastname: Van Goethem
authors.forename: Marianne
authors.initials: M
authors.lastname: Schwartz
authors.forename: Ann
authors.initials: A
authors.lastname: Löfgren
authors.forename: Bart
authors.initials: B
authors.lastname: Dermaut
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: John
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human