PMID:32618441

Gene: VWF

HGNCID:12726

Case:6 days old female infant

DiseaseAssertion:Type 2B

FamilyInfo:Her family history included no family members with low platelet levels or with bleeding diathesis.

ParentalGenotype(s):Negative for mutation by Sanger sequencing

CasePresentingHPOs:HP:0001873

CaseHPOFreeRext:Petechiae on her body and subependymal hemorrhage and bilateral intraventricular hemorrhage on US

GenotypingMethod:NGS

Gene:VWF

Variant:De Novo p.Val1316Met

HGVS:NP_000543.3:p.Val1316Met

ClinVarID:290

CAID:CA114127

gnomAD:6.20e-7

Case: Patient 1, Family A (Table 1.), F/49, Afro-Caribbean

DiseaseAssertion: VWD2B

FamilyInfo: Patient 2 (F/15, Afro-Caribbean) from same family A (Table 1.)

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeRext: BAT = 7, FVIII:C (IU/dL) = 28, VWF:Ag (IU/dL) = 35, VWF:Act (IU/dL) = 10

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).

PreviouslyPublished: NA

Gene: VWF

Variant: c.3946G > A p.(Val1316Met)

HGVS: NM_000552.5:c.3946G>A (p.Val1316Met)

ClinVarID: 290

CAID: CA114127

gnomAD:

Case: Patient 2, Family A (Table 1.), F/15, Afro-Caribbean

DiseaseAssertion: VWD2B

FamilyInfo: Patient 1 (F/49, Afro-Caribbean) from same family G. (Table 1.)

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeRext: BAT = 3, FVIII:C (IU/dL) = 50, VWF:Ag (IU/dL) = 57, VWF:Act (IU/dL) = 14

CaseNOTHPOs:

CaseNOTHPOFreeText: Blood group O+

CasePreviousTesting:

GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).

PreviouslyPublished: NA

Gene: VWF

Variant: c.3946G > A p.(Val1316Met)

HGVS: NM_000552.5:c.3946G>A (p.Val1316Met)

ClinVarID: 290

CAID: CA114127

gnomAD:

Gene:VWF

HGNCID:12726

Case:Preterm female newborn delivered by C/S

DiseaseAssertion:VWD Type 2B

FamilyInfo:Fig. 1 Father with VWD 2B and two paternal half-brothers diagnosed with hematomas after birth

ParentalGenotype(s):heterozygous carrier p.(Val1316Met) confirmed in the father, half-brothers were not tested

CasePresentingHPOs: HP:0001873, HP:0012147

CaseHPOFreeRext:Multiple hematomas, no cerebral hemorrhage

CaseNOTHPOs:HP:0030130

CaseNOTHPOFreeText:analyses showed reduced VWF activity levels (40% at postnatal day 7), whereas VWF antigen was normal (146% at postnatal day 7)

CasePreviousTesting:No . Gene:VWF

Variant:p.Val1316Met

HGVS:NM_000552.4:c.3946G>A

ClinVarID:290

CAID:CA114127

gnomAD:6.20e-7