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Eur J Hum Genet. 2014 Oct;22(10):1236-8. doi: 10.1038/ejhg.2014.9. Epub 2014 Feb 12.

A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.

Author information

1
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.
2
Department of Neurology, Dijon University Hospital, Dijon, France.
3
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.
4
1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] CNR-MAJ, Lille, Paris-Salpêtrière and Rouen University Hospitals, Paris, France.
5
Department of Pathology, Dijon University Hospital, Dijon, France.
6
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.
7
Department of otolaryngology and head and neck surgery, Dijon University Hospital, Dijon, France.
8
1] Inserm U1079, Rouen, France [2] IRIB, Normandie University, Rouen, France [3] Department of Genetics, Rouen University Hospital, Rouen, France.
9
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.
10
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.

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.

PMID:
24518837
PMCID:
PMC4169546
DOI:
10.1038/ejhg.2014.9
[Indexed for MEDLINE]
Free PMC Article

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