PB0212 - Patient with spontaneous and severe bleeding episodes diagnosed of Vascular Ehlers-Danlos Syndrome with a de novo pathogenic variant

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

shally Marcellini-Antonio, Sr., MD (she/her/hers)

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain

Co-Author(s)

IC

Irene Corrales-Insa

Hematologist
Congenital Coagulopathies Laboratory, Banc de Sang i Teixits, Barcelona, Spain.
Barcelona, Catalonia, Spain
PB

Perla Bandini

Hematologist
Congenital Coagulopathies Laboratory, Banc de Sang i Teixits, Barcelona, Spain.
Barcelona, Catalonia, Spain
NB

Nina Borrás

Hematologist
Congenital Coagulopathies Laboratory, Banc de Sang i Teixits, Barcelona, Spain.
Barcelona, Catalonia, Spain
LM

Laura Martin-fernández

Hematologist
Congenital Coagulopathies Laboratory, Banc de Sang i Teixits, Barcelona, Spain.
Barcelona, Catalonia, Spain
PG

Pilar Galán-Álvarez

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain
At

Ana torres-Tienza

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain
FV

Francisco Vidal- Pérez

Hematologist
Congenital Coagulopathies Laboratory, Banc de Sang i Teixits, Barcelona, Spain.
Barcelona, Catalonia, Spain
SV

Sandra Valencia-Castillo

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain
AG

Aranzazu García-Mateo

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain
CO

Carmen Olivier-Cornacchia

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain
JQ

José Antonio Queizán-Hernández

Hematologist
Department of Haematology, General Hospital of Segovia, Segovia, Spain.
Segovia, Castilla y Leon, Spain

Background: We present the case of a patient with severe bleeding episodes who required a genetic study for diagnosis. Preterm at birth, facial dysmorphia, bilateral ulnar clubhands, right clubfoot and fetal distress encephalopathy. At 2-months of age he required blood transfusions up to twice. At 26-year-old, was referred to our hospital after 3 episodes of severe spontaneous hematomas of the rectus abdominis muscle wall. Unfortunately, the patient died for spontaneous intestinal perforation.

Aims: To identify the molecular defect by Whole Exome Sequencing (WES) in a patient with recurrent bleeding

Methods: WES was done with the Illumina DNA Prep with Enrichment protocol in a NextSeq-500-system (Illumina). The bioinformatics analysis was performed with BWA Enrichment and VariantStudio (Illumina). The list of variants was filtered according to quality parameters, population frequency, and prediction of the functional impact on the protein.

Results: Initial coagulation studies were normal except for the PFA-100®System. ISTH-BAT-Score:16 (pathological>4 in adult males) and BEIGHTON-Score:7 (pathological>4). WES allowed the identification of a heterozygous variant in exon 44 of COL3A1: c.3230G>A, p.(Gly1077Asp) with an autosomal dominant inheritance. This variant was not previously described but other mutations affecting the same amino-acid had been classified as ‘likely pathogenic’ using ACMG Guidelines. The variant was validated by Sanger sequencing and family study revealed neither of the parents presented the same variant, concluding that it was a de novo mutation.

Conclusion(s): Vascular Ehlers Danlos syndrome (vEDS) is a rare autosomal dominant hereditary disorder, approximately 50% of cases by de novo pathogenic variants in the COL3A1 gene. Mutations in this gene predispose to a high risk of bleeding and death. The vEDS should be considered in patients with normal coagulation studies who present spontaneous rupture of a vessel or hollow organ with/without family history. In this context, WES is a useful strategy to identify the responsible mutation, allowing us a final diagnosis.