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

作者：Nicolas Gael; Jacquin Agnes; Thauvin Robinet Christel; Rovelet Lecrux Anne; Rouaud Olivier; Pottier Cyril; Aubriot Lorton Marie Helene; Rousseau Stephane; Wallon David; Duvillard Christian; Bejot Yannick; Frebourgl Thierry; Giroud Maurice; Campion Dominique; Hannequin Didier^*

来源：European Journal of Human Genetics, 2014, 22(10): 1236-1238.

DOI：10.1038/ejhg.2014.9

• IBGC
• Fahr%26apos
• s disease
• PDGFB
• PDGFRB
• de novo
• dementia

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%26apos; CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C%26gt;T (p.GIn147*), which was absent from the parents%26apos; 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%26gt;T mutation is located between two previously reported nonsense mutations, c.433C%26gt;T (p.GIn145*) and c.445C%26gt;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.

• 出版日期2014-10