title: Mutations in PTF1A are not a common cause for human VATER/VACTERL association or neural tube defects mirroring Danforth's short tail mouse.
abstract: Danforth's short tail (Sd) mutant mice exhibit defects of the neural tube and other abnormalities, which are similar to the human vertebral anomalies, anal atresia, cardiac defects, tracheosophageal fistula and/or esophageal atresia, renal and radial abnormalities, and limb defects (VATER/VACTERL) association, including defects of the hindgut. Sd has been shown to underlie ectopic gene expression of murine Ptf1a, which encodes pancreas-specific transcription factor 1A, due to the insertion of a retrotansposon in its 5' regulatory domain. In order to investigate the possible involvement of this gene in human VATER/VACTERL association and human neural tube defects (NTDs), a sequence analysis was performed. DNA samples from 103 patients with VATER/VACTERL and VATER/VACTERL‑like association, all presenting with anorectal malformations, and 72 fetuses with NTDs, where termination of pregnancy had been performed, were included in the current study. The complete PTF1A coding region, splice sites and 1.5 kb of the 5' flanking promotor region was sequenced. However, no pathogenic alterations were detected. The results of the present study do not support the hypothesis that high penetrant mutations in these regions of PTF1A are involved in the development of human VATER/VACTERL association or NTDs, although rare mutations may be detectable in larger patient samples.
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Gurung
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Greta
authors.initials: G
authors.lastname: Grosse
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Alina C
authors.initials: AC
authors.lastname: Hilger
authors.affiliation: Department of Pathology, Holy Family Hospital, Rawalpindi 46000, Pakistan.
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Nauman
authors.affiliation: Department of Neonatology, Children's Hospital, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.affiliation: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gembruch
authors.affiliation: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Waltraut M
authors.initials: WM
authors.lastname: Merz
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn D‑53127, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D001003:Anal Canal / Q000002:abnormalities* / Q000473:pathology; D000818:Animals; D001006:Anus, Imperforate / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D005333:Fetus; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011884:Radius / Q000002:abnormalities* / Q000473:pathology; D013131:Spine / Q000002:abnormalities* / Q000473:pathology; D014132:Trachea / Q000002:abnormalities* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors; C062602:transcription factor PTF1