A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.
Eur J Hum Genet
; 22(10): 1236-8, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24518837
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças dos Gânglios da Base
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Doenças da Laringe
/
Proteínas Proto-Oncogênicas c-sis
/
Distonia
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
França