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Partial deletions of the GRN gene are a cause of frontotemporal lobar degeneration.
Clot, Fabienne; Rovelet-Lecrux, Anne; Lamari, Foudil; Noël, Sandrine; Keren, Boris; Camuzat, Agnès; Michon, Agnès; Jornea, Ludmila; Laudier, Béatrice; de Septenville, Anne; Caroppo, Paola; Campion, Dominique; Cazeneuve, Cécile; Brice, Alexis; LeGuern, Eric; Le Ber, Isabelle.
Afiliação
  • Clot F; Département de Génétique, Cytogénétique et Embryologie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France, fabienne.clot@psl.aphp.fr.
Neurogenetics ; 15(2): 95-100, 2014 May.
Article em En | MEDLINE | ID: mdl-24469240
ABSTRACT
Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD). Most known GRN mutations are null mutations, such as nonsense and frameshift mutations, which create a premature stop codon resulting in loss of function of the progranulin protein. Complete or near-complete genomic GRN deletions have also been found in three families, but heterozygous partial deletions that remove only one or two exons have not been reported to date. In this study, we analysed three unrelated FTLD patients with low plasma progranulin levels but no point GRN mutations by multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF). We detected two heterozygous partial GRN deletions in two patients. One deletion removed exon 1 and part of intron 1. The second deletion was complex it removed 1,410 bp extending from the part of intron 1 to the part of exon 3, with a small 5-bp insertion at the breakpoint junction (c.-7-1121_159delinsGATCA). Our findings illustrate the usefulness of a quantitative analysis in addition to GRN gene sequencing for a comprehensive genetic diagnosis of FTLD, particularly in patients with low plasma progranulin levels.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deleção de Genes / Perda de Heterozigosidade / Peptídeos e Proteínas de Sinalização Intercelular / Degeneração Lobar Frontotemporal Limite: Humans / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deleção de Genes / Perda de Heterozigosidade / Peptídeos e Proteínas de Sinalização Intercelular / Degeneração Lobar Frontotemporal Limite: Humans / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article