title: Novel TGM5 mutations in acral peeling skin syndrome.
abstract: Acral peeling skin syndrome (APSS, MIM #609796) is a rare autosomal recessive disorder characterized by superficial exfoliation and blistering of the volar and dorsal aspects of hands and feet. The level of separation is at the junction of the stratum granulosum and stratum corneum. APSS is caused by mutations in the TGM5 gene encoding transglutaminase-5, which is important for structural integrity of the outermost epidermal layers. The majority of patients originate from Europe and carry a p.(Gly113Cys) mutation in TGM5. In this study, we report both European and non-European families carrying other mutations in the TGM5 gene. In 5 patients, we found 3 novel mutations: c.1001+2_1001+3del, c.1171G>A and c.1498C>T. To confirm their pathogenicity, we performed functional analyses with a transglutaminase activity assay, determined alternative splicing by reverse-transcribed PCR analysis and used databases and in silico prediction tools.
authors: Department of Dermatology, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW Research School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors: Jaap J A J
authors: JJ
authors: van der Velden
authors: Michel
authors: M
authors: van Geel
authors: Ruud G L
authors: RG
authors: Nellen
authors: Marcel F
authors: MF
authors: Jonkman
authors: John A
authors: JA
authors: McGrath
authors: Arti
authors: A
authors: Nanda
authors: Eli
authors: E
authors: Sprecher
authors: Maurice A M
authors: MA
authors: van Steensel
authors: W H Irwin
authors: WH
authors: McLean
authors: Andrew J
authors: AJ
authors: Cassidy
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005060:Europe; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D054643:INDEL Mutation; D007223:Infant; D007730:Kuwait; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D009426:Netherlands / Q000208:ethnology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012871:Skin Diseases / Q000151:congenital* / Q000201:enzymology / Q000235:genetics; D014162:Transfection; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D011994:Recombinant Proteins; C418703:transglutaminase 5; D011503:Transglutaminases
keywords: TGM5; acral peeling skin syndrome