Fiche publication
Date publication
octobre 2014
Journal
European journal of human genetics : EJHG
Auteurs
Membres identifiés du Cancéropôle Est :
Pr THAUVIN-ROBINET Christel
Tous les auteurs :
Nicolas G, Jacquin A, Thauvin-Robinet C, Rovelet-Lecrux A, Rouaud O, Pottier C, Aubriot-Lorton MH, Rousseau S, Wallon D, Duvillard C, Béjot Y, Frébourg T, Giroud M, Campion D, Hannequin D
Lien Pubmed
Résumé
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.
Mots clés
Basal Ganglia, pathology, Basal Ganglia Diseases, genetics, Brain, diagnostic imaging, Brain Diseases, genetics, Codon, Nonsense, DNA Topoisomerases, Type I, genetics, Dystonia, genetics, Exons, Female, Humans, Laryngeal Diseases, genetics, Pedigree, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-sis, genetics, RNA Splicing Factors, Ribonucleoprotein, U2 Small Nuclear, genetics, Tomography, X-Ray Computed, Young Adult
Référence
Eur J Hum Genet. 2014 10;22(10):1236-8
