Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics
We report our 5-year experience in neurofibromatosis type 1 prenatal diagnosis (PND): 205 PNDs in 146 women (chorionic villus biopsies, 88% or amniocentesis, 12%). The NF1 variant was present in 85 (41%) and absent in 122 (59%) fetuses. Among 205 pregnancies (207 fetuses), 135 were carried to term (119 unaffected and 16 NF1 affected children), 69 pregnancy terminations (affected fetuses), 2 miscarriages, and 1 in utero death. The majority of PND requests came from parents with sporadic NF1. We describe two PNDs in women with mosaic NF1. In both families, direct PND showed the absence of the maternal NF1 variant in the fetus. However, microsatellite markers analysis showed that the risk haplotype had been transmitted. These rare cases of germline mosaicism illustrate the pitfall of indirect PND. Our study illustrates the crucial consequences of PND for medical and genetic counseling decisions. We also point to the challenges of germline mosaics.
Authors
- Audrey Coustier
- Cécile Barbance
- Alice Goldenberg (ORCID: https://orcid.org/0000-0002-5864-9182)
- Béatrice Parfait (ORCID: https://orcid.org/0000-0002-2964-8666)
- Manuela Ye (ORCID: https://orcid.org/0000-0001-7839-9734)
- P. Wolkenstein (ORCID: https://orcid.org/0000-0001-8194-457X)
- Éric Pasmant (ORCID: https://orcid.org/0000-0002-1881-8762)
- Théodora Maillard
- Benoît Funalot (ORCID: https://orcid.org/0000-0001-6352-6518)
- Fanny Morice‐Picard (ORCID: https://orcid.org/0000-0002-4316-916X)
- Michel Vidaud
- Bérénice Hebrard
- Laurence Pacot (ORCID: https://orcid.org/0000-0001-7969-0558)
- Dominique Vidaud
- Ariane Lunati (ORCID: https://orcid.org/0000-0002-8425-431X)
- Albain Chansavang (ORCID: https://orcid.org/0000-0002-9835-2156)
- Djihad Hadjadj (ORCID: https://orcid.org/0000-0002-6916-5722)
- Ingrid Laurendeau (ORCID: https://orcid.org/0009-0003-5437-0015)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris-Est Créteil (FR)
- Université Paris Cité (FR)
- Hôpital Cochin (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Normandie Université (FR)
- Hôpitaux Universitaires Henri-Mondor (FR)
- Hydrologie Météorologie et Complexité (FR)
- Institut Cochin (FR)
- Université de Rouen Normandie (FR)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2024-09-08
- DOI
- https://doi.org/10.1038/s41525-024-00425-9
- Citations
- 5
- Primary Topic
- Neurofibromatosis and Schwannoma Cases
- Type
- article
- Field-Weighted Citation Impact
- 1.85
Funders
- European Commission
- Agence Nationale de la Recherche