Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant

Summary Germline mutations in tubulin beta class I (TUBB), which encodes one of the β‐tubulin isoforms, were previously associated with neurological and cutaneous abnormalities. Here, we describe the first case of inherited bone marrow (BM) failure, including marked thrombocytopenia, morphological a...

Full description

Saved in:
Bibliographic Details
Published in:British journal of haematology 2023-01, Vol.200 (2), p.222-228
Main Authors: Shah, Yash B., Lin, Ping, Chen, Stone, Zheng, Alan, Alcaraz, Wendy, Towne, Meghan C., Gabriel, Courtney, Bhoj, Elizabeth J., Lambert, Michele P., Olson, Timothy S., Frank, Dale M., Ellis, Colin A., Babushok, Daria V.
Format: Article
Language:English
Subjects:
6pLOH
Aplasia
Bone dysplasia
Bone marrow
bone marrow failure
Bone Marrow Failure Disorders - genetics
Chromosome Deletion
Chromosomes
Dysplasia
Germ Cells
Hematology
Hepatitis C
Heterozygosity
Humans
Immunosuppression
inherited thrombocytopenia
Isoforms
Loss of heterozygosity
Mutants
Pancytopenia
Pancytopenia - genetics
Ribavirin
Thrombocytopenia
Thrombocytopenia - genetics
TUBB
Tubulin
Tubulin - genetics
tubulinopathies
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Germline mutations in tubulin beta class I (TUBB), which encodes one of the β‐tubulin isoforms, were previously associated with neurological and cutaneous abnormalities. Here, we describe the first case of inherited bone marrow (BM) failure, including marked thrombocytopenia, morphological abnormalities, and cortical dysplasia, associated with a de novo p.D249V variant in TUBB. Mutant TUBB had abnormal cellular localisation in transfected cells. Following interferon/ribavirin therapy administered for transfusion‐acquired hepatitis C, severe pancytopenia and BM aplasia ensued, which was unresponsive to immunosuppression. Acquired chromosome arm 6p loss of heterozygosity was identified, leading to somatic loss of the mutant TUBB allele.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.18491