title: Generation of an iPSC line from a patient with GTP cyclohydrolase 1 (GCH1) deficiency: HDMC0061i-GCH1.
abstract: Fibroblasts from a female patient carrying a heterozygous variation in GTP cyclohydrolase 1 (GCH1; OMIM: 600225; HGNC: 4193; c.235_240del/p.(L79_S80del)), the rate-limiting enzyme of tetrahydrobiopterin (BH4) synthesis, were reprogrammed to iPSCs using the Cytotune®-iPS 2.0 Sendai Reprogramming Kit (Invitrogen) delivering the four reprogramming factors Oct3/4, Sox2, c-Myc and Klf4. Pluripotency of HDMC0061i-GCH1 was verified using immunohistochemistry and RT-PCR analysis. Cells differentiated spontaneously into the 3 germ layers in vitro and presented a normal karyotype. HDMC0061i-GCH1 represents the first model system to elucidate the pathomechanism underlying this rare metabolic disease and a useful tool for drug testing.
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: sabine.jung-klawitter@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Jung-Klawitter
authors.affiliation: Department of Human Genetics, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Ebersold
authors.affiliation: Department of Human Genetics, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D004252:DNA Mutational Analysis; D058732:Embryoid Bodies / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006136:GTP Cyclohydrolase / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059785:Karyotype; D000090062:Kruppel-Like Factor 4; D008856:Microscopy, Fluorescence; D010661:Phenylketonurias / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D006136:GTP Cyclohydrolase