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Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy.
Helderman-van den Enden, A T J M; de Jong, R; den Dunnen, J T; Houwing-Duistermaat, J J; Kneppers, A L J; Ginjaar, H B; Breuning, M H; Bakker, E.
Afiliación
  • Helderman-van den Enden AT; Center for Human and Clinical Genetics, Leiden UniversityMedical Center, Leiden, the Netherlands.
Clin Genet ; 75(5): 465-72, 2009 May.
Article en En | MEDLINE | ID: mdl-19475718
The presence of multiple affected offspring from apparently non-carrier parents is caused by germ line mosaicism. Although germ line mosaicism has been reported for many diseases, figures for recurrence risks are known for only a few of them. In X-linked Duchenne and Becker muscular dystrophies (DMD/BMD), the recurrence risk for non-carrier females due to germ line mosaicism has been estimated to be between 14% and 20% (95% confidence interval 3-30) if the risk haplotype is transmitted. In this study, we have analyzed 318 DMD/BMD cases in which the detected mutation was de novo with the aim of obtaining a better estimate of the 'true' number of germ line mosaics and a more precise recurrence risk. This knowledge is essential for genetic counseling. Our data indicate a recurrence risk of 8.6% (4.8-12.2) if the risk haplotype is transmitted, but there is a remarkable difference between proximal (15.6%) (4.1-27.0) and distal (6.4%) (2.1-10.6) deletions. Overall, most mutations originated in the female. Deletions occur more often on the X chromosome of the maternal grandmother, whereas point mutations occur on the X chromosome of the maternal grandfather. In unhaplotyped de novo DMD/BMD families, the risk of recurrence of the mutation is 4.3%.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación de Línea Germinal / Distrofia Muscular de Duchenne / Mosaicismo Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Clin Genet Año: 2009 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Dinamarca
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación de Línea Germinal / Distrofia Muscular de Duchenne / Mosaicismo Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Clin Genet Año: 2009 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Dinamarca