COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.
Journal
Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
12
01
2022
received:
22
11
2021
accepted:
09
02
2022
pubmed:
13
2
2022
medline:
27
4
2022
entrez:
12
2
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35150448
doi: 10.1002/pd.6113
pmc: PMC10434296
mid: NIHMS1922001
doi:
Substances chimiques
COL4A1 protein, human
0
COL4A2 protein, human
0
Collagen Type IV
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
601-610Subventions
Organisme : NINDS NIH HHS
ID : R01 NS096173
Pays : United States
Organisme : NIH HHS
ID : R01NS096173
Pays : United States
Organisme : NIH HHS
ID : R01NS096173
Pays : United States
Informations de copyright
© 2022 John Wiley & Sons Ltd.
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