title: A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.
abstract: Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] Department of Genetics, Rouen University Hospital, Rouen, France [4] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France.
authors: Gaël
authors: G
authors: Nicolas
authors: Department of Neurology, Dijon University Hospital, Dijon, France.
authors: Agnès
authors: A
authors: Jacquin
authors: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Grand-Est, Hôpital d'Enfants, Dijon University Hospital, Dijon, France.
authors: Christel
authors: C
authors: Thauvin-Robinet
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France.
authors: Anne
authors: A
authors: Rovelet-Lecrux
authors: Department of Neurology, Dijon University Hospital, Dijon, France.
authors: Olivier
authors: O
authors: Rouaud
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France.
authors: Cyril
authors: C
authors: Pottier
authors: Department of Pathology, Dijon University Hospital, Dijon, France.
authors: Marie-Hélène
authors: MH
authors: Aubriot-Lorton
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France.
authors: Stéphane
authors: S
authors: Rousseau
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France [4] Department of Neurology, Rouen University Hospital, Rouen, France.
authors: David
authors: D
authors: Wallon
authors: Department of otolaryngology and head and neck surgery, Dijon University Hospital, Dijon, France.
authors: Christian
authors: C
authors: Duvillard
authors: Department of Neurology, Dijon University Hospital, Dijon, France.
authors: Yannick
authors: Y
authors: Béjot
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] Department of Genetics, Rouen University Hospital, Rouen, France.
authors: Thierry
authors: T
authors: Frébourg
authors: Department of Neurology, Dijon University Hospital, Dijon, France.
authors: Maurice
authors: M
authors: Giroud
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France [4] Department of Research, Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.
authors: Dominique
authors: D
authors: Campion
authors: 1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] Department of Genetics, Rouen University Hospital, Rouen, France [4] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France [5] Department of Neurology, Rouen University Hospital, Rouen, France.
authors: Didier
authors: D
authors: Hannequin
mesh_terms: D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging; D001927:Brain Diseases / Q000235:genetics; D018389:Codon, Nonsense; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D004421:Dystonia / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D007818:Laryngeal Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000378:metabolism; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D020574:Proto-Oncogene Proteins c-sis; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C088050:SF3A1 protein, human; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human