Mosaicism and prenatal diagnosis options: insights from retinoblastoma

Autor: Isabelle Aerts, Marion Gauthier-Villars, Catherine Dehainault, Lisa Golmard, Julien Tarabeux, Dominique Stoppa-Lyonnet, Nathalie Cassoux, Gaël A Millot, Claude Houdayer, Agathe Charpin, Anthony Laugé
Přispěvatelé: Institut Curie [Paris], Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Département d'oncologie pédiatrique [Institut Curie, Paris], Université Paris Descartes - Paris 5 (UPD5), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by RETINOSTOP and Programme Incitatif et Coopératif ‘Rétinoblastome’ Institut Curie., millot, gael, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Parents
0301 basic medicine
Proband
MESH: Mutation Rate
[SDV.GEN] Life Sciences [q-bio]/Genetics
030105 genetics & heredity
Germline
Mutation Rate
Prenatal Diagnosis
MESH: Germ-Line Mutation
Genetics (clinical)
MESH: Heterozygote
Genetics
education.field_of_study
MESH: Genetic Testing
Mosaicism
Retinoblastoma
3. Good health
Retinoblastoma Binding Proteins
Medical genetics
MESH: Genetic Counseling
Heterozygote
medicine.medical_specialty
Offspring
Ubiquitin-Protein Ligases
Population
Short Report
Genetic Counseling
Prenatal diagnosis
Biology
03 medical and health sciences
medicine
Humans
Genetic Testing
MESH: Retinoblastoma
MESH: Prenatal Diagnosis
education
Germ-Line Mutation
MESH: Parents
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
Siblings
Cytogenetics
medicine.disease
MESH: Ubiquitin-Protein Ligases
MESH: Siblings
MESH: Retinoblastoma Binding Proteins
030104 developmental biology
Zdroj: European Journal of Human Genetics
European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (3), pp.381-383. ⟨10.1038/ejhg.2016.174⟩
European Journal of Human Genetics, 2017, 25 (3), pp.381-383. ⟨10.1038/ejhg.2016.174⟩
ISSN: 1018-4813
1476-5438
DOI: 10.1038/ejhg.2016.174⟩
Popis: International audience; In sporadic cases, a post-zygotic mutational event signifies a somatic mosaicism in the affected child only, which implies that these mutations affect only a portion of the body. Therefore siblings do not need follow-up. On the other hand, a pre-zygotic mutation transmitted by an unaffected mosaic parent implies recurrent risks in offspring. To better estimate the contribution of pre- and post-zygotic events, we analysed 124 consecutive bilateral retinoblastoma probands, carrying a heterozygous RB1 pathogenic variant and their unaffected, non-carrier parents. In order to evaluate somatic mosaicism in blood, the deleterious RB1 pathogenic variant identified in the proband, was searched for in the unaffected parents, using targeted deep sequencing. Observed recurrences, which represent an estimation of germline and somatic mosaicisms, were recorded and computed in the sibships. Deep sequencing revealed one mosaic-unaffected parent out of 124 tested couples, which provides an estimation of the maximal risk of recurrence, due to parental mosaicism, at 0.4%. Follow-up in the sibships showed one recurrence, providing a maximal recurrence risk, due to parental mosaicism, at 0.8%. Two different statistical strategies led to close estimates (0.4 and 0.8% risks) which appeared 266-533-fold higher, as compared with the general population. These recurrence estimates could be considered when counselling couples with retinoblastoma or diseases with a high de novo mutation rate.
Databáze: OpenAIRE
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