ACTN1-related thrombocytopenia

Identification of novel families for phenotypic characterization

Roberta Bottega, Caterina Marconi, Michela Faleschini, Gabriele Baj, Claudia Cagioni, Alessandro Pecci, Tommaso Pippucci, Ugo Ramenghi, Simonetta Pardini, Loretta Ngu, Carlo Baronci, Shinji Kunishima, Carlo L. Balduini, Marco Seri, Anna Savoia, Patrizia Noris

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 α-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.

Original languageEnglish
Pages (from-to)869-872
Number of pages4
JournalBlood
Volume125
Issue number5
DOIs
Publication statusPublished - Jan 29 2015

Fingerprint

Thrombocytopenia
Actinin
Thrombopoietin
Gene encoding
Amino Acid Substitution
Bioinformatics
Platelets
Computational Biology
Platelet Count
Genes
Differential Diagnosis
Substitution reactions
Hemorrhage
Amino Acids
Mutation
Serum

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

ACTN1-related thrombocytopenia : Identification of novel families for phenotypic characterization. / Bottega, Roberta; Marconi, Caterina; Faleschini, Michela; Baj, Gabriele; Cagioni, Claudia; Pecci, Alessandro; Pippucci, Tommaso; Ramenghi, Ugo; Pardini, Simonetta; Ngu, Loretta; Baronci, Carlo; Kunishima, Shinji; Balduini, Carlo L.; Seri, Marco; Savoia, Anna; Noris, Patrizia.

In: Blood, Vol. 125, No. 5, 29.01.2015, p. 869-872.

Research output: Contribution to journalArticle

Bottega, R, Marconi, C, Faleschini, M, Baj, G, Cagioni, C, Pecci, A, Pippucci, T, Ramenghi, U, Pardini, S, Ngu, L, Baronci, C, Kunishima, S, Balduini, CL, Seri, M, Savoia, A & Noris, P 2015, 'ACTN1-related thrombocytopenia: Identification of novel families for phenotypic characterization', Blood, vol. 125, no. 5, pp. 869-872. https://doi.org/10.1182/blood-2014-08-594531
Bottega, Roberta ; Marconi, Caterina ; Faleschini, Michela ; Baj, Gabriele ; Cagioni, Claudia ; Pecci, Alessandro ; Pippucci, Tommaso ; Ramenghi, Ugo ; Pardini, Simonetta ; Ngu, Loretta ; Baronci, Carlo ; Kunishima, Shinji ; Balduini, Carlo L. ; Seri, Marco ; Savoia, Anna ; Noris, Patrizia. / ACTN1-related thrombocytopenia : Identification of novel families for phenotypic characterization. In: Blood. 2015 ; Vol. 125, No. 5. pp. 869-872.
@article{4557955cabf64894bebe3e72e4633b0d,
title = "ACTN1-related thrombocytopenia: Identification of novel families for phenotypic characterization",
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 α-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.",
author = "Roberta Bottega and Caterina Marconi and Michela Faleschini and Gabriele Baj and Claudia Cagioni and Alessandro Pecci and Tommaso Pippucci and Ugo Ramenghi and Simonetta Pardini and Loretta Ngu and Carlo Baronci and Shinji Kunishima and Balduini, {Carlo L.} and Marco Seri and Anna Savoia and Patrizia Noris",
year = "2015",
month = "1",
day = "29",
doi = "10.1182/blood-2014-08-594531",
language = "English",
volume = "125",
pages = "869--872",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - ACTN1-related thrombocytopenia

T2 - Identification of novel families for phenotypic characterization

AU - Bottega, Roberta

AU - Marconi, Caterina

AU - Faleschini, Michela

AU - Baj, Gabriele

AU - Cagioni, Claudia

AU - Pecci, Alessandro

AU - Pippucci, Tommaso

AU - Ramenghi, Ugo

AU - Pardini, Simonetta

AU - Ngu, Loretta

AU - Baronci, Carlo

AU - Kunishima, Shinji

AU - Balduini, Carlo L.

AU - Seri, Marco

AU - Savoia, Anna

AU - Noris, Patrizia

PY - 2015/1/29

Y1 - 2015/1/29

N2 - 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 α-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.

AB - 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 α-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.

UR - http://www.scopus.com/inward/record.url?scp=84921806112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921806112&partnerID=8YFLogxK

U2 - 10.1182/blood-2014-08-594531

DO - 10.1182/blood-2014-08-594531

M3 - Article

VL - 125

SP - 869

EP - 872

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -