title: Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome.
abstract: Approximately 20% of Beckwith-Wiedemann syndrome (BWS) cases are caused by mosaic paternal uniparental disomy of chromosome 11 (pUPD11). Although pUPD11 is usually limited to the short arm of chromosome 11, a small minority of BWS cases show genome-wide mosaic pUPD (GWpUPD). These patients show variable clinical features depending on mosaic ratio, imprinting status of other chromosomes, and paternally inherited recessive mutations. To date, there have been no reports of a mosaic GWpUPD patient with an autosomal recessive disease caused by a paternally inherited recessive mutation. Here, we describe a patient concurrently showing the clinical features of BWS and autosomal recessive cystinuria. Genetic analyses revealed that the patient has mosaic GWpUPD and an inherited paternal homozygous mutation in SLC7A9. This is the first report indicating that a paternally inherited recessive mutation can cause an autosomal recessive disease in cases of GWpUPD mosaicism. Investigation into recessive mutations and the dysregulation of imprinting domains is critical in understanding precise clinical conditions of patients with mosaic GWpUPD.
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtsuka
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Higashimoto
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Jozaki
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshinaga
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takama
authors.affiliation: Department of Pediatric Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kubota
authors.affiliation: Department of Pathology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yatsuki
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Joh
authors.affiliation: Nishikyushu University, Saga, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: K-i
authors.initials: KI
authors.lastname: Yoshiura
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Soejima
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000235:genetics*; D003555:Cystinuria / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D014463:Ultrasonography; D024182:Uniparental Disomy
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489857:SLC3A1 protein, human; C499489:SLC7A9 protein, human
keywords: Beckwith-Wiedemann syndrome; SLC3A1; SLC7A9; cystinuria; genome-wide paternal uniparental disomy mosaicism