Inherited bleeding disorders

Gene: ADAMTS13

Comment on mode of inheritance: Changed MOI from 'BOTH monoallelic and biallelic' to 'BIALLELIC' - only biallelic cases with homozygous or compound heterozygous variants described. Heterozygous carriers are asymptomatic.

Created: 23 Mar 2021, 11:39 a.m. | Last Modified: 23 Mar 2021, 11:39 a.m.

Panel Version: 1.157

Green List (high evidence)

Current level of evidence and expert review, High level of confidence as disease-causing gene. Proven in 3 unrelated pedigrees via cosegregation analysis or less than 3 or 1 large pedigree supported with functional studies (animal model). Ready for clinical reporting. Previous comments from expert reviewer observed in the NIHRBR-RD BRIDGE cohort.

Created: 9 Aug 2017, 12:31 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thrombotic disorder; Thrombotic thrombocytopenic purpura, familial

Publications

• 11586351

Variants in this GENE are reported as part of current diagnostic practice

Comment on phenotypes: added phenotype from expert review

Created: 9 Aug 2017, 12:54 p.m.

Comment on mode of pathogenicity: changed loss-of-function variants exception, since loss of function tier 1 transcript_ablation, splice_donor_variant, splice_acceptor_variant, stop_gained, frameshift_variant, stop_lost or initiator_codon_variant/start_lost) variants are pathogenic in this gene.

Created: 1 Jun 2017, 1:44 p.m.

Comment on list classification: Expert review green, and multiple cases reported with different variants

Created: 1 Jun 2017, 1:41 p.m.

Comment on publications: Added publications to support gene is involved in the disorder(s) in 3 or more unrelated cases

Created: 1 Jun 2017, 1:36 p.m.

Comment on publications: added publication suggested by external reviewer

Created: 1 Jun 2017, 1:23 p.m.

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital Thrombotic Thrombocytopenic Purpura, or Schulman-Upshaw Syndrome

Publications

• Levy, G. G., Nichols, W. C., Lian, E. C., Foroud, T., McClintick, J. N., McGee, B. M., Yang, A. Y., Slemieniak, D. R., Stark, K. R., Gruppo, R., Sarode, R., Shurin, S. B., Chandrasekaran, V., Stabler, S. P., Sabio, H., Bouhassira, E. E., Upshaw, J. D., Jr., Ginsburg, D., Tsai, H.-M. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413: 488-494, 2001.

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments