ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization

2.50
Hdl Handle:
http://hdl.handle.net/11287/593937
Title:
ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization
Authors:
Bottega, R.; Marconi, C.; Faleschini, M.; Baj, G.; Cagioni, C.; Pecci, A.; Pippucci, T.; Ramenghi, U.; Pardini, S.; Ngu, Loretta; Baronci, C.; Kunishima, S.; Balduini, C. L.; Seri, M.; Savoia, A.; Noris, P.
Abstract:
Inherited thrombocytopenias (ITs) are a heterogeneous group of syndromic and nonsyndromic diseases caused by mutations affecting different genes. Alterations of ACTN1, the gene encoding for alpha-actinin 1, have recently been identified in a few families as being responsible for a mild form of IT (ACTN1-related thrombocytopenia; ACTN1-RT). To better characterize this disease, we screened ACTN1 in 128 probands and found 10 (8 novel) missense heterozygous variants in 11 families. Combining bioinformatics, segregation, and functional studies, we demonstrated that all but 1 amino acid substitution had deleterious effects. The clinical and laboratory findings of 31 affected individuals confirmed that ACTN1-RT is a mild macrothrombocytopenia with low risk for bleeding. Low reticulated platelet counts and only slightly increased serum thrombopoietin levels indicated that the latest phases of megakaryopoiesis were affected. Given its relatively high frequency in our cohort (4.2%), ACTN1-RT has to be taken into consideration in the differential diagnosis of ITs.
Citation:
Blood. 2015 Jan 29;125(5):869-72.
Publisher:
Blood
Journal:
Blood
Issue Date:
29-Jan-2015
URI:
http://hdl.handle.net/11287/593937
DOI:
10.1182/blood-2014-08-594531
PubMed ID:
25361813
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25361813/
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1528-0020
Appears in Collections:
2015 RD&E publications; Clinical Haematology

Full metadata record

DC FieldValue Language
dc.contributor.authorBottega, R.en
dc.contributor.authorMarconi, C.en
dc.contributor.authorFaleschini, M.en
dc.contributor.authorBaj, G.en
dc.contributor.authorCagioni, C.en
dc.contributor.authorPecci, A.en
dc.contributor.authorPippucci, T.en
dc.contributor.authorRamenghi, U.en
dc.contributor.authorPardini, S.en
dc.contributor.authorNgu, Lorettaen
dc.contributor.authorBaronci, C.en
dc.contributor.authorKunishima, S.en
dc.contributor.authorBalduini, C. L.en
dc.contributor.authorSeri, M.en
dc.contributor.authorSavoia, A.en
dc.contributor.authorNoris, P.en
dc.date.accessioned2016-01-19T12:37:37Zen
dc.date.available2016-01-19T12:37:37Zen
dc.date.issued2015-01-29en
dc.identifier.citationBlood. 2015 Jan 29;125(5):869-72.en
dc.identifier.issn1528-0020en
dc.identifier.pmid25361813en
dc.identifier.doi10.1182/blood-2014-08-594531en
dc.identifier.urihttp://hdl.handle.net/11287/593937en
dc.description.abstractInherited thrombocytopenias (ITs) are a heterogeneous group of syndromic and nonsyndromic diseases caused by mutations affecting different genes. Alterations of ACTN1, the gene encoding for alpha-actinin 1, have recently been identified in a few families as being responsible for a mild form of IT (ACTN1-related thrombocytopenia; ACTN1-RT). To better characterize this disease, we screened ACTN1 in 128 probands and found 10 (8 novel) missense heterozygous variants in 11 families. Combining bioinformatics, segregation, and functional studies, we demonstrated that all but 1 amino acid substitution had deleterious effects. The clinical and laboratory findings of 31 affected individuals confirmed that ACTN1-RT is a mild macrothrombocytopenia with low risk for bleeding. Low reticulated platelet counts and only slightly increased serum thrombopoietin levels indicated that the latest phases of megakaryopoiesis were affected. Given its relatively high frequency in our cohort (4.2%), ACTN1-RT has to be taken into consideration in the differential diagnosis of ITs.en
dc.language.isoengen
dc.publisherBlooden
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25361813/en
dc.titleACTN1-related thrombocytopenia: identification of novel families for phenotypic characterizationen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalBlooden
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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