Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics.

IF 4.7 2区医学 Q1 GENETICS & HEREDITY NPJ Genomic Medicine Pub Date : 2024-09-08 DOI:10.1038/s41525-024-00425-9

Laurence Pacot, Dominique Vidaud, Manuela Ye, Albain Chansavang, Audrey Coustier, Theodora Maillard, Cécile Barbance, Ingrid Laurendeau, Bérénice Hébrard, Ariane Lunati-Rozie, Benoît Funalot, Pierre Wolkenstein, Michel Vidaud, Alice Goldenberg, Fanny Morice-Picard, Djihad Hadjadj, Béatrice Parfait, Eric Pasmant

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Abstract

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.

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1 型神经纤维瘤病的产前诊断和种系杂交的陷阱。

我们报告了 5 年来在神经纤维瘤病 1 型产前诊断（PND）方面的经验：146 名妇女的 205 例产前诊断（绒毛膜活检，88% 或羊膜腔穿刺术，12%）。85 个（41%）胎儿存在 NF1 变异，122 个（59%）胎儿不存在 NF1 变异。在 205 例妊娠（207 个胎儿）中，135 例足月（119 个未受影响的胎儿和 16 个受 NF1 影响的胎儿），69 例终止妊娠（受影响的胎儿），2 例流产，1 例胎死宫内。大多数 PND 申请来自散发性 NF1 患儿的父母。我们描述了两个镶嵌型 NF1 女性的 PND。在这两个家庭中，直接 PND 均显示胎儿中不存在母体 NF1 变异。然而，微卫星标记分析表明，风险单倍型已经传播。这些罕见的种系嵌合病例说明了间接 PND 的隐患。我们的研究说明了 PND 对医疗和遗传咨询决策的重要影响。我们还指出了种系镶嵌所面临的挑战。

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.