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Table 4 Pathogenic and likely pathogenic variants identified in genes associated with autosomal recessive and X-linked recessive bleeding and platelet disorders

From: Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders

Case

Position

Gene

Ref

Alt

Genotype

HGMD

Effect a

Haematological HPO terms

Other HPO terms

Classification:

Variant

Phenotype

B200286

3:148881737

HPS3

G

C

C|C

Yes

Abnormal splicing

Bleeding with minor or no trauma, subcutaneous haemorrhage, menorrhagia, postpartum haemorrhage, impaired ADP-induced platelet aggregation, impaired epinephrine-induced platelet aggregation, epistaxis, prolonged bleeding after surgery, prolonged bleeding after dental extraction, increased mean platelet volume.

Hypothyroidism, visual impairment, nystagmus, albinism.

PV

Explained

B200412

3:148858819

HPS3

T

TA

T|TA

No

Frameshift

Impaired epinephrine-induced platelet aggregation, bleeding with minor or no trauma, subcutaneous haemorrhage, epistaxis, menorrhagia, prolonged bleeding after surgery, abnormal dense granules.

Ocular albinism.

LPV

Possibly explained

3:148876539

HPS3

G

A

G|A

No

W593a

 

LPV

B200068

10:103827041

HPS6

C

G

C|G

No

L604V

Increased mean platelet volume.

Congenital cataract, strabismus, maternal diabetes.

LPV

Possibly explained

10:103827554

HPS6

C

G

C|G

No

L775V

LPV

B200196

X:48542673

WAS

C

T

T

Yes

T45M

Thrombocytopenia, abnormal bleeding, decreased mean platelet volume, abnormal platelet shape.

Recurrent infections.

PV

Explained

B200725

X:48544145

WAS

T

C

C

Yes

F128S

Monocytosis, neutrophilia, thrombocytopenia, leukocytosis, subcutaneous haemorrhage, gastrointestinal haemorrhage.

 

PV

Explained

B200443

X:138633272

F9

G

A

A

Yes

R191H

Reduced factor IX activity, impaired ADP-induced platelet aggregation, bleeding with minor or no trauma, spontaneous haematomas, abnormal number of dense granules.

 

PV

Partially explained

B200452

X:154124407

F8

C

G

G

Yes

S2125T

Reduced factor VIII activity, persistent bleeding after trauma, prolonged bleeding after surgery, prolonged bleeding after dental extraction, bleeding requiring red cell transfusion, impaired collagen-induced platelet aggregation, bleeding with minor or no trauma, joint haemorrhage, abnormal platelet shape, abnormal number of dense granules.

 

PV

Partially explained

B200772

X:154176011

F8

A

G

G

No

F692S

Reduced factor VIII activity, bruising susceptibility, impaired ADP-induced platelet aggregation, impaired collagen-induced platelet aggregation, impaired thromboxane A2 agonist-induced platelet aggregation, impaired ristocetin-induced platelet aggregation, impaired arachidonic acid-induced platelet aggregation, impaired thrombin-induced platelet aggregation, abnormal platelet granules, bleeding with minor or no trauma.

 

LPV

Possibly partially explained

  1. Alt: alternative; Ref: reference.
  2. aEffect considered relative to the Consensus Coding Sequence (CCDS) for each gene.