• Bénédicte Sudrié-Arnaud, Florent Marguet, Sophie Patrier, Jelena Martinovic, Ferielle Louillet, Françoise Broux, Françoise Charbonnier, Hélène Dranguet, Sophie Coutant, Myriam Vezain, Raphaël Lanos, Abdellah Tebani, Maria Fuller, Foudil Lamari, Pascal Chambon, Anne-Claire Brehin, Laetitia Trestard, Isabelle Tournier, Stéphane Marret, Eric Verspyck, Annie Laquerrière, and Soumeya Bekri.
• Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76000, France.
• Clin. Chim. Acta. 2018 Jun 1; 481: 1-8.

PurposesHydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. In addition, this approach is time consuming. We have developed a next-generation sequencing (NGS) panel to investigate metabolic causes of NIHF, ascites, and polyhydramnios associated to another fetal abnormality.MethodsThe hydrops fetalis (HydFet) panel was designed to cover the coding regions and flanking intronic sequences of 41 genes. A retrospective study of amniotic fluid samples from 40 subjects was conducted. A prospective study was subsequently initiated, and six samples were analyzed using the NGS panel.ResultsFive IEM diagnoses were made using the HydFet panel (Niemann-Pick type C (NPC), Barth syndrome, HNF1Β deficiency, GM1 gangliosidosis, and Gaucher disease). This analysis also allowed the identification of 8p sequence triplication in an additional case.ConclusionNGS combined with robust bioinformatics analyses is a useful tool for identifying the causative variants of NIHF. Subsequent functional characterization of the protein encoded by the altered gene and morphological studies may confirm the diagnosis. This paradigm shift allows a significant improvement of IEM diagnosis in NIHF.Copyright © 2018 Elsevier B.V. All rights reserved.

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