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...
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| Veröffentlicht in: | British journal of haematology 2023-01, Vol.200 (2), p.222-228 |
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| container_title | British journal of haematology |
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| creator | 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. |
| description | 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. |
| doi_str_mv | 10.1111/bjh.18491 |
| format | Article |
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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.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.18491</identifier><identifier>PMID: 36207145</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>British journal of haematology, 2023-01, Vol.200 (2), p.222-228</ispartof><rights>2022 British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>2023 British Society for Haematology and John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-55d5869b13bf47926e5be8a8b93bfed4424ff5e74c6105abf5623f076735982b3</citedby><cites>FETCH-LOGICAL-c3531-55d5869b13bf47926e5be8a8b93bfed4424ff5e74c6105abf5623f076735982b3</cites><orcidid>0000-0002-1745-0353 ; 0000-0003-0439-402X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjh.18491$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.18491$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36207145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Yash B.</creatorcontrib><creatorcontrib>Lin, Ping</creatorcontrib><creatorcontrib>Chen, Stone</creatorcontrib><creatorcontrib>Zheng, Alan</creatorcontrib><creatorcontrib>Alcaraz, Wendy</creatorcontrib><creatorcontrib>Towne, Meghan C.</creatorcontrib><creatorcontrib>Gabriel, Courtney</creatorcontrib><creatorcontrib>Bhoj, Elizabeth J.</creatorcontrib><creatorcontrib>Lambert, Michele P.</creatorcontrib><creatorcontrib>Olson, Timothy S.</creatorcontrib><creatorcontrib>Frank, Dale M.</creatorcontrib><creatorcontrib>Ellis, Colin A.</creatorcontrib><creatorcontrib>Babushok, Daria V.</creatorcontrib><title>Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>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.</description><subject>6pLOH</subject><subject>Aplasia</subject><subject>Bone dysplasia</subject><subject>Bone marrow</subject><subject>bone marrow failure</subject><subject>Bone Marrow Failure Disorders - genetics</subject><subject>Chromosome Deletion</subject><subject>Chromosomes</subject><subject>Dysplasia</subject><subject>Germ Cells</subject><subject>Hematology</subject><subject>Hepatitis C</subject><subject>Heterozygosity</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>inherited thrombocytopenia</subject><subject>Isoforms</subject><subject>Loss of heterozygosity</subject><subject>Mutants</subject><subject>Pancytopenia</subject><subject>Pancytopenia - genetics</subject><subject>Ribavirin</subject><subject>Thrombocytopenia</subject><subject>Thrombocytopenia - genetics</subject><subject>TUBB</subject><subject>Tubulin</subject><subject>Tubulin - genetics</subject><subject>tubulinopathies</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O4zAURi3ECArDghdAltjAIuAb_yRZUsRAR0izgXVkJzfUVRIX26Hq2-OZAguk8cbW1blH1vcRcgrsCtK5NqvlFZSigj0yA65kloOAfTJjjBUZMFEekqMQVowBZxIOyCFXOStAyBnpF-MSvY3YUuNGpIP23m1op20_eaQbG5dp1ngXl94NxjXb6NY4Wk3bCWl09AX90Nu0GSczpQc1GDVteh0CXdCLp-f5_JK-aW_1GH-SH53uA5583Mfk-dfd0-1D9vjnfnF785g1XHLIpGxlqSoD3HSiqHKF0mCpS1OlAbZC5KLrJBaiUcCkNp1UOe9YoQouqzI3_Jhc7Lxr714nDLEebGiw7_WIbgp1XuQcFKTlhJ5_Q1du8mP6XaKU4Ektq0Rd7qgURAgeu3rtbYpqWwOr_1ZQpwrqfxUk9uzDOJkB2y_yM_MEXO-Aje1x-39TPf_9sFO-A6w9jxk</recordid><startdate>202301</startdate><enddate>202301</enddate><creator>Shah, Yash B.</creator><creator>Lin, Ping</creator><creator>Chen, Stone</creator><creator>Zheng, Alan</creator><creator>Alcaraz, Wendy</creator><creator>Towne, Meghan C.</creator><creator>Gabriel, Courtney</creator><creator>Bhoj, Elizabeth J.</creator><creator>Lambert, Michele P.</creator><creator>Olson, Timothy S.</creator><creator>Frank, Dale M.</creator><creator>Ellis, Colin A.</creator><creator>Babushok, Daria V.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1745-0353</orcidid><orcidid>https://orcid.org/0000-0003-0439-402X</orcidid></search><sort><creationdate>202301</creationdate><title>Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-55d5869b13bf47926e5be8a8b93bfed4424ff5e74c6105abf5623f076735982b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>6pLOH</topic><topic>Aplasia</topic><topic>Bone dysplasia</topic><topic>Bone marrow</topic><topic>bone marrow failure</topic><topic>Bone Marrow Failure Disorders - genetics</topic><topic>Chromosome Deletion</topic><topic>Chromosomes</topic><topic>Dysplasia</topic><topic>Germ Cells</topic><topic>Hematology</topic><topic>Hepatitis C</topic><topic>Heterozygosity</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>inherited thrombocytopenia</topic><topic>Isoforms</topic><topic>Loss of heterozygosity</topic><topic>Mutants</topic><topic>Pancytopenia</topic><topic>Pancytopenia - genetics</topic><topic>Ribavirin</topic><topic>Thrombocytopenia</topic><topic>Thrombocytopenia - genetics</topic><topic>TUBB</topic><topic>Tubulin</topic><topic>Tubulin - genetics</topic><topic>tubulinopathies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shah, Yash B.</creatorcontrib><creatorcontrib>Lin, Ping</creatorcontrib><creatorcontrib>Chen, Stone</creatorcontrib><creatorcontrib>Zheng, Alan</creatorcontrib><creatorcontrib>Alcaraz, Wendy</creatorcontrib><creatorcontrib>Towne, Meghan C.</creatorcontrib><creatorcontrib>Gabriel, Courtney</creatorcontrib><creatorcontrib>Bhoj, Elizabeth J.</creatorcontrib><creatorcontrib>Lambert, Michele P.</creatorcontrib><creatorcontrib>Olson, Timothy S.</creatorcontrib><creatorcontrib>Frank, Dale M.</creatorcontrib><creatorcontrib>Ellis, Colin A.</creatorcontrib><creatorcontrib>Babushok, Daria V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shah, Yash B.</au><au>Lin, Ping</au><au>Chen, Stone</au><au>Zheng, Alan</au><au>Alcaraz, Wendy</au><au>Towne, Meghan C.</au><au>Gabriel, Courtney</au><au>Bhoj, Elizabeth J.</au><au>Lambert, Michele P.</au><au>Olson, Timothy S.</au><au>Frank, Dale M.</au><au>Ellis, Colin A.</au><au>Babushok, Daria V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2023-01</date><risdate>2023</risdate><volume>200</volume><issue>2</issue><spage>222</spage><epage>228</epage><pages>222-228</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>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.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>36207145</pmid><doi>10.1111/bjh.18491</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-1745-0353</orcidid><orcidid>https://orcid.org/0000-0003-0439-402X</orcidid></addata></record> |
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| 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 |
| title | Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant |
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