title: POLG exon 22 skipping induced by different mechanisms in two unrelated cases of Alpers syndrome.
abstract: The POLG genes were sequenced in two unrelated patients presenting with Alpers syndrome. The novel c.3626_3629dupGATA and the c.3643+2T>C alleles were associated in trans with p.A467T and p.[W748S;E1143G], respectively. POLG transcripts from skin fibroblasts showed complete exon 22 skipping for patient 2, but surprisingly partial exon 22 skipping from the c.3626_3629dupGATA for patient 1. The creation of a putative exonic splicing silencer could be responsible for the splicing anomaly observed in patient 1. Both c.3643+2T>C and c.3626_3629dupGATA create a premature termination codon and a low polymerase γ activity in skin fibroblasts is responsible for the severe phenotype in these patients.
authors.affiliation: Centre de Biologie et de Pathologie Est - CHU Lyon, Service des Maladies Héréditaires du Métabolisme, 69677 Bron, France. benedicte.mousson-de-camaret@chu-lyon.fr
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mousson de Camaret
authors.forename: Maïté
authors.initials: M
authors.lastname: Chassagne
authors.forename: Martine
authors.initials: M
authors.lastname: Mayençon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Padet
authors.forename: Hervé
authors.initials: H
authors.lastname: Crehalet
authors.forename: Pascale
authors.initials: P
authors.lastname: Clerc-Renaud
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouvet
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Zabot
authors.forename: François
authors.initials: F
authors.lastname: Rivier
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
authors.forename: Dominique
authors.initials: D
authors.lastname: Bozon
mesh_terms: D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D012326:RNA Splicing; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human