COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage - Sorbonne Université Access content directly
Journal Articles Prenatal Diagnosis Year : 2022

COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage

Thibault Coste
Catherine Vincent-Delorme
  • Function : Author
Morgane Stichelbout
  • Function : Author
Louise Devisme
Fanny Pelluard
  • Function : Author
Chaker Aloui
  • Function : Author
Anne-Louise Leutenegger
  • Function : Author
Douglas Gould
  • Function : Author
Elisabeth Tournier-Lasserve
  • Function : Author
Anne‐louise Leutenegger
  • Function : Author
Jean‐marie Jouannic

Abstract

Background: Variants of COL4A1/COL4A2 genes have been reported in fetal intracranial hemorrhage (ICH) cases but their prevalence and characteristics have not been established in a large series of fetuses. Fetal neonatal alloimmune thrombocytopenia is a major acquired ICH factor but the prevalence and characteristics of inherited platelet disorder (IPD) gene variants leading to thrombocytopenia are unknown. Herein, we screened COL4A1/COL4A2 and IPD genes in a large series of ICH fetuses. Methods: A cohort of 194 consecutive ICH fetuses were first screened for COL4A1/COL4A2 variants. We manually curated a list of 64 genes involved in IPD and investigated them in COL4A1/COL4A2 negative fetuses, using exome sequencing data from 101 of these fetuses. Result: Pathogenic variants of COL4A1/COL4A2 genes were identified in 36 fetuses (19%). They occurred de novo in 70% of the 32 fetuses for whom parental DNA was available. Pathogenic variants in two megakaryopoiesis genes (MPL and MECOM genes) were identified in two families with recurrent and severe fetal ICH, with variable extraneurological pathological features. Conclusion: Our study emphasizes the genetic heterogeneity of fetal ICH and the need to screen both COL4A1/COL4A2 and IPD genes in the etiological investigation of fetal ICH to allow proper genetic counseling.

Dates and versions

hal-04577702 , version 1 (16-05-2024)

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Thibault Coste, Catherine Vincent-Delorme, Morgane Stichelbout, Louise Devisme, Antoinette Gelot, et al.. COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage. Prenatal Diagnosis, 2022, 42 (5), pp.601-610. ⟨10.1002/pd.6113⟩. ⟨hal-04577702⟩
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